Assessment of patterns of infiltration and relapse of patients with glioblastoma of the occipital lobe

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Tumours arising in different neuroanatomical sites may have specific pathways for infiltration. This study aims to review the infiltration and relapse sites for the occipital lobe glioblastoma to determine sites at risk, and potentially improve future target volume delineation protocols. Method: Patients with occipital lobe glioblastoma and managed with EORTC-NCIC Protocol were identified through a prospective database. Based on MRI analysis a qualitative description of sites of tumour infiltration and subsequent relapse was performed. These were categorized into neuroanatomical subsites adjacent to the occipital lobe: Level 1 related to origin gyrus; Level 2 adjacent gyral subsites; Level 3 subsites involved distant regions. These spatial patterns were assessed in relation to three major white matter tracts: inferior longitudinal fasciculus, cingulum, and corpus callosum. Results: 46 patients were analysed. At diagnosis, 20 patients (43.5%) had medial occipital lobe involvement and 26 (56.5%) had lateral involvement. Level 2 and level 3 infiltration were observed in 33 (71.7%) and 27 (58.7%) of patients. Relapse occurred in 43 patients (93.5%), 28% at level 1, 77% at level 2, and 98% at level 3. Level 3 relapse sites included the trigone (70%), splenium (30%), and anterior temporal lobe (35%). Lateral tumours relapsed more commonly in the trigone (75% vs 52.6%) and anterior temporal lobe (50% vs 15.8%, p =0.026), while medial tumours more frequently involved the splenium (47.3% vs 16.7%, p =0.046). Conclusions: Infiltration and relapse of glioblastoma involving the occipital lobe suggests distinct neuroanatomical patterns which may guide radiation therapy target volume delineation. Glioblastoma Occipital lobe Radiotherapy Infiltration patterns Relapse patterns Figures Figure 1 Figure 2 Introduction Glioblastoma is the most common primary brain tumour in adults, and despite subtle advancements in treatment over the past decade, only marginal improvements in survival have been attained [ 1 ]. Glioblastoma exhibits aggressive infiltration and recurrence post-surgical resection and adjuvant treatment. The neural connectome, the network of white matter tracts within the brain, has been proposed as a plausible route for tumour spread [ 1 ]. This may account for glioblastoma progression distant from the initial tumour site, as these pathways connect anatomically distinct brain regions. Despite an aggressive multimodal treatment approach, the prognosis for glioblastoma remains poor, with median overall survival (OS) ranging from 14 to 18 months [ 2 – 5 ]. Since 2005, numerous novel therapeutic agents have been trialled in the adjuvant setting; however, none have demonstrated a survival benefit [ 2 , 6 , 7 ]. These findings underscore the importance of optimising current treatment protocols and reviewing current paradigms. The current standard of care for newly diagnosed glioblastoma involves adjuvant fractionated radiotherapy combined with temozolomide based on the EORTC-NCIC Protocol [ 8 , 9 ]. Despite advances in our understanding of glioblastoma infiltration, as well as improvements in neuroimaging and radiotherapy techniques, this protocol has remained largely unchanged. Radiotherapy target volume delineation protocols for glioblastoma are largely based on autopsy studies conducted in the 1980s, which demonstrated microscopic tumour infiltration extending beyond 20 mm from the primary tumour mass [ 10 , 11 ]. These studies predated the era of magnetic resonance imaging (MRI) and other advanced neuroradiological techniques. However, they still continue to form the foundation of standard protocols that apply a uniform 15–20 mm isotropic expansion around the tumour bed [ 8 ]. This is suboptimal given evidence that marginal recurrences remain uncommon in protocols that explore margin reduction [ 12 ]. Potentially, wide treatment margins, encompassing cortical tissue may contribute to cerebral atrophy and late neurocognitive morbidity in patients who are longer term survivors. Technological advances in neuroimaging such as reduced slice thickness, three-dimensional reconstruction, and T2-FLAIR sequencing have significantly improved initial tumour delineation. Non-enhancing tumour infiltration is increasingly recognised on MRI and amino acid positron emission tomography (PET) at sites distant from the primary contrast-enhancing lesion. In parallel, diffusion tensor imaging (DTI), already used clinically for tractography to guide neurosurgical procedures, has been explored in the context of the structural connectome; with some studies suggesting it may assist in detecting occult tumour invasion along white matter tracts [ 13 ]. This study aims to provide clinical data supporting the concept of tumour infiltration and spread along anatomically connected brain regions by examining glioblastoma involving one region with low tumour incidence, the occipital lobe [ 14 ], with a focus on patterns of infiltration and subsequent tumour relapse. Methods This retrospective study analysed consecutive adult patients (≥ 18 years) with newly diagnosed glioblastoma referred to the Neuro-Oncology Multidisciplinary Tumour Board between January 2008 and December 2023. Data for this study was stored in a prospectively maintained database, approved by the Northern Sydney Local Health District Human Research Ethics Committee (reference LNR/15/HAWKE355). Patients were eligible for inclusion if they had histologically confirmed glioblastoma (WHO Grade 4, isocitrate dehydrogenase (IDH) wildtype involving the occipital lobe and were managed according to the EORTC-NCIC protocol (adjuvant radiotherapy to 60Gy with temozolomide). Exclusion criteria consisted of patients with incomplete baseline or follow-up imaging and survival data. Clinical data were extracted from the institutional electronic medical records and ethics-approved database, encompassing: (1) demographic characteristics; (2) tumour-specific parameters including histopathology, imaging characteristics, O6-Methylguanine-DNA methyltransferase (MGMT) promoter methylation status; (3) treatment details including extent of surgical resection, radiation therapy dose/fractionation, temozolomide use (4) quantitative radiologic outcomes derived from diagnostic and relapse MRI; and (5) survival endpoints (dates of progression and mortality). Categorization of site of infiltration and relapse Three-dimensional tumour volumetric segmentation was performed manually using Eclipse™ treatment planning software (Varian Medical Systems, Palo Alto, CA). Volumetric assessments were conducted on both T1-gadolinium enhanced MRI and T2-weighted FLAIR sequences at both preoperative diagnosis, and at confirmed progression. For all measurements, the residual tumour volume was delineated on MRI scans co-registered with computed tomography (CT) imaging to improve anatomical accuracy. These MRI volumes were then categorized to neuroanatomical subsites adjacent to the occipital lobe designating three levels of infiltration (Fig. 1 ): Level 1 origin subsites related to the involved gyrus: laterally the inferior, middle, and superior occipital gyri; and medially the lingual gyrus. Level 2 adjacent gyral subsites connected to the origin regions: medial occipitotemporal gyrus, lateral occipitotemporal gyrus, and cingulate gyrus. Level 3 distant subsites involved deeper extension: trigone of lateral ventricle, anterior temporal lobe and the splenium of the corpus callosum. These spatial patterns were also assessed in relation to three adjacent major white matter tracts: inferior longitudinal fasciculus, cingulum and corpus callosum Statistical considerations The primary endpoint involved a comprehensive qualitative description of site of infiltration / relapse, and frequency of these sites in relation to initial tumour subsite within the occipital lobe. These endpoints were analysed using descriptive statistics, and p values were calculated with Fischer’s Exact Test given small sample sizes, with statistical significance set at p = 0.05. Secondary endpoints included median OS and relapse free survival (RFS), and the association with tumour subsite and known prognostic factors. Statistical analysis was performed using Jamovi and IBM SPSS software. Kaplan-Meier survival analysis was conducted, and Cox proportional univariate hazards regression was used to evaluate the predictive value of measured variables, with statistical significance set at p = 0.05. Results A total of 46 patients with primary occipital lobe glioblastoma were managed in the study period and available for analysis. 44 patients have deceased with the two surviving patients progression-free at 21 and 45 months, respectively. Median OS was 17.4 months (95% CI: 15.1–19.9), and median RFS was 10.1 months (95% CI: 8.4–13.0). Patient characteristics are detailed in Table 1 . Table 1 Baseline patient, tumour, and resection characteristics Characteristic Median (IQR a ) or n (%) Age at diagnosis Median (IQR a ) Years 60.7 (14.3) Initial ECOG b performance status 0 1 2 3 4 13 (28.2%) 25 (54.3%) 7 (15.2%) 1 (2.2%) 0 (0%) MGMT c Methylation Status Unmethylated Methylated Result unavailable 16 (34.7%) 15 (32.6%) 15 (32.6%) Ki-67 Proliferation Index 0-25% 26-50% 51-75% 76-100% Result unavailable Median Ki-67 (IQR) 14 (30.4%) 21 (45.6%) 3 (6.5%) 2 (4.3%) 6 (13.0%) 30% (21.3%) Extent of resection Biopsy Subtotal Gross total 3 (6.5%) 18 (39.1%) 25 (54.3%) a IQR, interquartile range; b ECOG, Eastern Cooperative Oncology Group; c MGMT, O6-methylguanine-DNA methyltransferase. Infiltration patterns At diagnosis, tumours were localised to either the medial occipital lobe in 20 patients (43.5%) or the lateral occipital lobe in 26 patients (56.5%). Level 2 infiltration was present in 33 patients (71.7%) and level 3 in 27 patients (58.7%). In medial tumours, 15 patients (75%) had level 2 and 11 patients (55%) had level 3 infiltration. In lateral tumours, 18 patients (69.2%) had level 2 and 16 patients (61.5%) had level 3 infiltration. There was no statistically significant difference in the presence of level 2 or 3 infiltration between medial and lateral subsites ( p = 0.75 and p = 0.76, respectively). Among those with level 3 infiltration, medial tumours involved the trigone in 7 patients (63.6%), splenium in 4 patients (36.4%), and anterior temporal lobe in 1 patient (9.1%). In lateral tumours, the trigone was involved in 15 patients (93.8%), splenium in 1 patient (6.3%), and anterior temporal lobe in 3 patients (18.8%). While trigone involvement appeared more frequent in lateral tumours and splenial involvement more common in medial tumours, none of these differences reached statistical significance ( p = 0.15 for trigone, p = 0.15 for splenium and p = 0.62 for anterior temporal lobe). See Table 2. Table 2 Infiltration patterns, comparing medial and lateral (level 1) origin occipital lobe glioblastoma Variable Medial (n=20) Lateral (n=26) Total n p-value a Level 2 infiltration 15 (75.0%) 18 (69.2%) 33 (71.7%) 0.75 Level 3 infiltration 11 (55.0%) 16 (61.5%) 27 (58.7%) 0.76 Level 3 subsite infiltration Trigone 7 (63.6%) 15 (93.8%) 22 (81.4%) 0.15 Splenium 4 (36.4%) 1 (6.3%) 5 (18.5%) 0.15 Anterior temporal lobe 1 (9.1%) 3 (18.8%) 4 (14.8%) 0.62 a p-values correspond to statistical comparisons of infiltration rates between medial and lateral tumour locations. Relapse patterns Relapse occurred in 43 patients (93.5%), including 19 patients (95%) with medial tumours and 24 patients (92.3%) with lateral tumours. Of the relapsed patients, involvement in medial tumours included level 1 in 4 patients (21.1%), level 2 in 13 patients (68.4%), and level 3 in 18 patients (94.7%). Involvement in lateral tumours included level 1 in 8 patients (33.3%), level 2 in 20 patients (83.3%), and level 3 in 24 patients (100%). Of the relapsed patients there was no statistically significant difference in involvement of level 3 at relapse based on initial tumour localization, 18 patients (94.7%) for medial tumours and 24 (100%) patients for lateral tumours, with a p value of 0.44, respectively. At specific level 3 subsites, medial tumours involved the trigone in 10 patients (52.6%), the splenium in 9 patients (47.3%), and the anterior temporal lobe in 3 patients (15.8%). Lateral tumours involved the trigone in 18 patients (75%), the splenium in 4 patients (16.7%), and the anterior temporal lobe in 12 patients (50%). These differences were statistically significant for splenium ( p = 0.046) and anterior temporal lobe ( p = 0.026), but not for trigone (p = 0.198). See Table 3, and Figure 2 which compares level 3 site specific relapse based on origin . Table 3 Relapse patterns, comparing medial and lateral (level 1) origin occipital lobe glioblastoma Variable Medial (n=19) Lateral (n=24) Total n p-value a Level 1 involvement 4 (21.1%) 8 (33.3%) 12 (27.9%) - Level 2 involvement 13 (68.4%) 20 (83.3%) 33 (76.7%) 0.295 Level 3 involvement 18 (94.7%) 24 (100%) 42 (97.7%) 0.440 Level 3 subsite infiltration Trigone 10 (52.6%) 18 (75%) 28 (66.7%) 0.198 Splenium 9 (47.3%) 4 (16.7%) 13 (31.0%) 0.046 Anterior temporal lobe 3 (15.8%) 12 (50%) 15 (35.7%) 0.026 a p-values correspond to statistical comparisons of relapse site involvement based on medial and lateral tumour origin. Association of occipital lobe subsite with survival outcome Survival outcomes in relation to tumour localization were not statistically significant. Median OS was 16.3 months (95% CI: 13.1–24.0) for medial tumours; and 18.0 months (95% CI: 15.1–23.6) for lateral tumours, with a hazard ratio (HR) of 0.95 (95% CI: 0.51–1.77; p = 0.876). Median RFS was 10.4 months (95% CI: 8.9–14.3) for medial tumours and 9.3 months (95% CI: 7.7–17.9) for lateral tumours, with an HR of 0.95 (95% CI: 0.52–1.75; p = 0.869; log-rank p = 0.87). Other factors and interaction with survival outcome Higher ECOG scores at diagnosis tended to be associated with worse OS: 19.4 months for ECOG 0 (95% CI: 12.9–26.0), 17.1 months for ECOG 1 (95% CI: 14.7–19.6), and 11.4 months for ECOG 2 (95% CI: 11.0–11.7). Incremental increases in ECOG were confirmed to be statistically significant in terms of association with worse OS (HR: 1.72; 95% CI: 1.14–2.58; p = 0.010). Although not statistically significant, relapse-free survival (RFS) also tended to decline with increasing ECOG scores . Each one-point increase in ECOG was associated with a non-significant increase in relapse risk (HR: 1.43; 95% CI: 0.96–2.13; p = 0.082). MGMT promoter methylation status was available for 31 patients: 16 (51.6%) were unmethylated and 15 (48.4%) methylated. Median OS was longer in the methylated group at 23.6 months (95% CI: 15.7–31.6) compared to 14.3 months (95% CI: 10.8–17.7) in the unmethylated group. Methylation was associated with statistically significant improved OS (HR: 0.29; 95% CI: 0.12–0.69; p = 0.005). RFS was also longer in the methylated group, with a median of 17.9 months (95% CI: 8.0–27.8) versus 8.7 months (95% CI: 7.5–9.9) in the unmethylated group. The risk of relapse was likewise improved and statistically significant in methylated tumours (HR: 0.18; 95% CI: 0.07–0.47; p < 0.001). Higher Ki-67 expression was associated with poorer outcomes. Every 10% increase in Ki-67 corresponded to statistically significant shorter median OS (HR: 1.58; 95% CI: 1.28–1.96; p < 0.001) and shorter RFS (HR: 1.43; 95% CI: 1.17–1.76; p < 0.001). In regards to extent of surgical resection, there was no association with either overall or relapse-free survival. OS was 15.7 months (95% CI: 6.3–25.2) for biopsy, 15.5 months (95% CI: 8.3–22.6) for subtotal resection, and 18.1 months (95% CI: 14.0–22.3) for gross total resection. There was no statistically significant difference in OS when biopsy was compared to subtotal resection (HR: 0.72; 95% CI: 0.21–2.47; p = 0.597) or gross total resection (HR: 0.58; 95% CI: 0.17–1.95; p = 0.376). Median RFS was 13.1 months (95% CI: 4.1–22.1) for biopsy, 10.2 months (95% CI: 9.3–11.2) for subtotal resection, and 8.9 months (95% CI: 5.9–11.8) for gross total resection. As with OS, there was no statistically significant difference in RFS when comparing subtotal resection (HR: 1.03; 95% CI: 0.30–3.52; p = 0.966) or gross total resection (HR: 0.80; 95% CI: 0.23–2.73; p = 0.721) to biopsy. Discussion This study provides a focused analysis of occipital lobe glioblastoma, a relatively uncommon tumour location[ 14 ], and examines the patterns of initial infiltration, relapse, and survival outcomes according to tumour subsite within the occipital lobe. Although the patient sample population is small in numbers there was a reasonable distribution of medial (20 patients) and lateral (26 patients) occipital tumours. Tumour infiltration at diagnosis was common beyond the occipital lobe in both medial and lateral occipital subsites. With over 70% of patients demonstrating level 2 infiltration and 58.7% exhibiting level 3 infiltration. Interestingly, analysis of relapse patterns suggested that progression in this cohort of occipital glioblastoma most frequently occurred at distant sites. High rates of recurrence were observed at level 2 and particularly at level 3, regardless of whether the tumour originated at a medial or lateral subsite within the occipital lobe. Only 21.1% of medial and 33.3% of lateral tumours relapsed at level 1. In contrast, level 2 involvement at relapse was seen in over two-thirds (68.4%) of medial tumours and 83.3% of lateral tumours, while level 3 involvement occurred in nearly all cases (94.7% and 100%, respectively). Indicating that within this cohort local or marginal tumour relapse was relatively uncommon. Additionally, there was no statistically significant difference in survival outcomes for the extent of surgery, thus suggesting the high risk of distant infiltration is more prominent than local disease. It may support the hypothesis that relapse occurs in predictable pathways rather than isotropic extension from the original contrast enhancing mass. Between occipital subsites there were statistically significant differences in relapse patterns, involving specific level 3 subsites. Medial tumours relapsed more frequently in the splenium and less frequently in the anterior temporal lobe compared to lateral tumours. Although not statistically significant, trigone involvement seemed to be more prominent amongst lateral tumours (75% vs 52.6%). Although the findings on analysis of infiltration were not statistically significant, they correlated with relapse patterns where splenium involvement appeared more common in medial tumours and trigone involvement more common in lateral tumours. These findings imply potential subsite-specific routes of tumour progression and may reflect differences in white matter connectivity or patterns. Medially the major white matter tracts such as cingulum and corpus callosum emerge from this region and thus extend into splenium. Laterally the inferior longitudinal fasciculus extends towards the trigone and anterior temporal lobe. See Fig. 2 for radiological examples. The OS of 17.4 months and RFS of 10.1 months are in keeping with reported survival outcomes for glioblastoma [ 3 – 5 ]. This suggests that occipital localization of glioblastoma may not have a substantially different prognosis compared to tumours in other brain regions. Despite the anatomical distinctions in relapse patterns mentioned above, no statistically significant survival difference between medial and lateral occipital tumours was demonstrated. The limitations of this study include its retrospective design and undoubtedly its relatively small sample size. Additionally, subgroup analysis was somewhat incomplete, certain variables such as MGMT promoter methylation status for instance were not available for all patients. Furthermore given the somewhat rarity of occipital lobe glioblastoma comparative literature is limited, which restricts broader contextualisation of our findings. Conclusion This study contributes valuable insight into the behaviour of occipital lobe glioblastoma. The high frequency of level 3 progression involving deep structures such as the trigone, splenium and anterior temporal lobe suggest that traditional isotropic margin expansion in radiotherapy based solely on the initial tumour location may underestimate the true extent of disease. This underscores the importance of further investigating the incorporation of likely pathways of spread, particularly white matter tracts, into radiotherapy planning. Declarations Competing Interests: The authors have no relevant financial or non-financial interests to disclose. Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki. Consent to participate: Informed consent was obtained from all individual participants included in the study. Consent to publish: The authors affirm that human research participants provided informed consent for publication of de-identified data. Funding: The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Author Contribution M.S. developed the manuscript, contributed to data collection, performed statistical analyses, and contributed to data interpretation. C.K.L. contributed to statistical analyses, contributed to data interpretation, and reviewed the manuscript. M.B. conceived and designed the study, contributed to data collection and neuroanatomical site characterisation, and provided manuscript commentary and critical revision. All authors reviewed and approved the final manuscript. Data Availability The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. References Salvalaggio A, Pini L, Bertoldo A, Corbetta M (2024) Glioblastoma and brain connectivity: the need for a paradigm shift. 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J Neurosurg 68(5):698–704 Gebhardt BJ, Dobelbower MC, Ennis WH, Bag AK, Markert JM, Fiveash JB (2014) Patterns of failure for glioblastoma multiforme following limited-margin radiation and concurrent temozolomide. Radiat Oncol 9(1):130 Henssen D, Meijer F, Verburg FA, Smits M (2023) Challenges and opportunities for advanced neuroimaging of glioblastoma. Br J Radiol 96(1141):20211232 Larjavaara S, Mäntylä R, Salminen T, Haapasalo H, Raitanen J, Jääskeläinen J et al (2007) Incidence of gliomas by anatomic location. Neurooncology 9(3):319–325 Statements & Declarations Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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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16:29:57","extension":"html","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":73966,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8277737/v1/3932ecf2f9b3fc1fb07ce32c.html"},{"id":97932921,"identity":"704866ba-6682-470f-915b-c43ecd798d3b","added_by":"auto","created_at":"2025-12-11 00:47:40","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":304261,"visible":true,"origin":"","legend":"\u003cp\u003eNeuroanatomical levels of infiltration\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8277737/v1/610865e9353f9abd84edf3a4.png"},{"id":97932919,"identity":"f49d546e-39c7-4216-8d7e-e6948a632643","added_by":"auto","created_at":"2025-12-11 00:47:40","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":325719,"visible":true,"origin":"","legend":"\u003cp\u003eAxial T1-weighted gadolinium-enhanced MRI; examples of infiltration and relapse patterns\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e\u003cem\u003eA\u003c/em\u003e\u003c/sup\u003e\u003cem\u003eMedial tumour with relapse involving cingulum\u003cbr\u003e\n\u003c/em\u003e\u003csup\u003e\u003cem\u003eB\u003c/em\u003e\u003c/sup\u003e\u003cem\u003eLateral tumour infiltrating towards trigone, with relapse involving inferior longitudinal fasciculus\u003c/em\u003e\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8277737/v1/ed9af56b3f4892aef25e6296.png"},{"id":98797922,"identity":"0f5a2647-a525-4627-a5d0-5104b47209af","added_by":"auto","created_at":"2025-12-22 14:04:07","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1502511,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8277737/v1/592d4df3-2d55-4109-a042-6ab70819297e.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Assessment of patterns of infiltration and relapse of patients with glioblastoma of the occipital lobe","fulltext":[{"header":"Introduction","content":"\u003cp\u003eGlioblastoma is the most common primary brain tumour in adults, and despite subtle advancements in treatment over the past decade, only marginal improvements in survival have been attained [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Glioblastoma exhibits aggressive infiltration and recurrence post-surgical resection and adjuvant treatment. The neural connectome, the network of white matter tracts within the brain, has been proposed as a plausible route for tumour spread [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. This may account for glioblastoma progression distant from the initial tumour site, as these pathways connect anatomically distinct brain regions.\u003c/p\u003e\u003cp\u003eDespite an aggressive multimodal treatment approach, the prognosis for glioblastoma remains poor, with median overall survival (OS) ranging from 14 to 18 months [\u003cspan additionalcitationids=\"CR3 CR4\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Since 2005, numerous novel therapeutic agents have been trialled in the adjuvant setting; however, none have demonstrated a survival benefit [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. These findings underscore the importance of optimising current treatment protocols and reviewing current paradigms.\u003c/p\u003e\u003cp\u003eThe current standard of care for newly diagnosed glioblastoma involves adjuvant fractionated radiotherapy combined with temozolomide based on the EORTC-NCIC Protocol [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Despite advances in our understanding of glioblastoma infiltration, as well as improvements in neuroimaging and radiotherapy techniques, this protocol has remained largely unchanged.\u003c/p\u003e\u003cp\u003eRadiotherapy target volume delineation protocols for glioblastoma are largely based on autopsy studies conducted in the 1980s, which demonstrated microscopic tumour infiltration extending beyond 20 mm from the primary tumour mass [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. These studies predated the era of magnetic resonance imaging (MRI) and other advanced neuroradiological techniques. However, they still continue to form the foundation of standard protocols that apply a uniform 15\u0026ndash;20 mm isotropic expansion around the tumour bed [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. This is suboptimal given evidence that marginal recurrences remain uncommon in protocols that explore margin reduction [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Potentially, wide treatment margins, encompassing cortical tissue may contribute to cerebral atrophy and late neurocognitive morbidity in patients who are longer term survivors.\u003c/p\u003e\u003cp\u003eTechnological advances in neuroimaging such as reduced slice thickness, three-dimensional reconstruction, and T2-FLAIR sequencing have significantly improved initial tumour delineation. Non-enhancing tumour infiltration is increasingly recognised on MRI and amino acid positron emission tomography (PET) at sites distant from the primary contrast-enhancing lesion. In parallel, diffusion tensor imaging (DTI), already used clinically for tractography to guide neurosurgical procedures, has been explored in the context of the structural connectome; with some studies suggesting it may assist in detecting occult tumour invasion along white matter tracts [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThis study aims to provide clinical data supporting the concept of tumour infiltration and spread along anatomically connected brain regions by examining glioblastoma involving one region with low tumour incidence, the occipital lobe [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], with a focus on patterns of infiltration and subsequent tumour relapse.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis retrospective study analysed consecutive adult patients (\u0026ge;\u0026thinsp;18 years) with newly diagnosed glioblastoma referred to the Neuro-Oncology Multidisciplinary Tumour Board between January 2008 and December 2023. Data for this study was stored in a prospectively maintained database, approved by the Northern Sydney Local Health District Human Research Ethics Committee (reference LNR/15/HAWKE355).\u003c/p\u003e\u003cp\u003ePatients were eligible for inclusion if they had histologically confirmed glioblastoma (WHO Grade 4, isocitrate dehydrogenase (IDH) wildtype involving the occipital lobe and were managed according to the EORTC-NCIC protocol (adjuvant radiotherapy to 60Gy with temozolomide). Exclusion criteria consisted of patients with incomplete baseline or follow-up imaging and survival data.\u003c/p\u003e\u003cp\u003eClinical data were extracted from the institutional electronic medical records and ethics-approved database, encompassing: (1) demographic characteristics; (2) tumour-specific parameters including histopathology, imaging characteristics, O6-Methylguanine-DNA methyltransferase (MGMT) promoter methylation status; (3) treatment details including extent of surgical resection, radiation therapy dose/fractionation, temozolomide use (4) quantitative radiologic outcomes derived from diagnostic and relapse MRI; and (5) survival endpoints (dates of progression and mortality).\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eCategorization of site of infiltration and relapse\u003c/h2\u003e\u003cp\u003eThree-dimensional tumour volumetric segmentation was performed manually using Eclipse\u0026trade; treatment planning software (Varian Medical Systems, Palo Alto, CA). Volumetric assessments were conducted on both T1-gadolinium enhanced MRI and T2-weighted FLAIR sequences at both preoperative diagnosis, and at confirmed progression. For all measurements, the residual tumour volume was delineated on MRI scans co-registered with computed tomography (CT) imaging to improve anatomical accuracy.\u003c/p\u003e\u003cp\u003eThese MRI volumes were then categorized to neuroanatomical subsites adjacent to the occipital lobe designating three levels of infiltration (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e):\u003c/p\u003e\u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003e\u003cem\u003eLevel 1\u003c/em\u003e origin subsites related to the involved gyrus: laterally the inferior, middle, and superior occipital gyri; and medially the lingual gyrus.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003e\u003cem\u003eLevel 2\u003c/em\u003e adjacent gyral subsites connected to the origin regions: medial occipitotemporal gyrus, lateral occipitotemporal gyrus, and cingulate gyrus.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003e\u003cem\u003eLevel 3\u003c/em\u003e distant subsites involved deeper extension: trigone of lateral ventricle, anterior temporal lobe and the splenium of the corpus callosum.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e\u003cp\u003eThese spatial patterns were also assessed in relation to three adjacent major white matter tracts: inferior longitudinal fasciculus, cingulum and corpus callosum\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eStatistical considerations\u003c/h3\u003e\n\u003cp\u003eThe primary endpoint involved a comprehensive qualitative description of site of infiltration / relapse, and frequency of these sites in relation to initial tumour subsite within the occipital lobe. These endpoints were analysed using descriptive statistics, and p values were calculated with Fischer\u0026rsquo;s Exact Test given small sample sizes, with statistical significance set at p\u0026thinsp;=\u0026thinsp;0.05.\u003c/p\u003e\u003cp\u003eSecondary endpoints included median OS and relapse free survival (RFS), and the association with tumour subsite and known prognostic factors. Statistical analysis was performed using Jamovi and IBM SPSS software. Kaplan-Meier survival analysis was conducted, and Cox proportional univariate hazards regression was used to evaluate the predictive value of measured variables, with statistical significance set at p\u0026thinsp;=\u0026thinsp;0.05.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 46 patients with primary occipital lobe glioblastoma were managed in the study period and available for analysis. 44 patients have deceased with the two surviving patients progression-free at 21 and 45 months, respectively. Median OS was 17.4 months (95% CI: 15.1\u0026ndash;19.9), and median RFS was 10.1 months (95% CI: 8.4\u0026ndash;13.0). Patient characteristics are detailed in \u003cem\u003eTable 1\u003c/em\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e1\u003c/strong\u003e Baseline patient, tumour, and resection characteristics\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristic\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian (IQR\u003csup\u003ea\u003c/sup\u003e) or n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003eAge at diagnosis\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Median (IQR\u003csup\u003ea\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003eYears\u003c/p\u003e\n \u003cp\u003e60.7 \u0026nbsp; \u0026nbsp; \u0026nbsp; (14.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003eInitial ECOG\u003csup\u003eb\u003c/sup\u003e performance status\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 0\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 1\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 2\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 3\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e13 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; (28.2%)\u003c/p\u003e\n \u003cp\u003e25 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; (54.3%)\u003c/p\u003e\n \u003cp\u003e7 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; (15.2%)\u003c/p\u003e\n \u003cp\u003e1 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; (2.2%)\u003c/p\u003e\n \u003cp\u003e0 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eMGMT\u003csup\u003ec\u003c/sup\u003e Methylation Status\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Unmethylated\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Methylated\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Result unavailable\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e16 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; (34.7%)\u003c/p\u003e\n \u003cp\u003e15 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; (32.6%)\u003c/p\u003e\n \u003cp\u003e15 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; (32.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003eKi-67 Proliferation Index\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 0-25%\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 26-50%\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 51-75%\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 76-100%\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Result unavailable\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Median Ki-67 (IQR)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e14 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; (30.4%)\u003c/p\u003e\n \u003cp\u003e21 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; (45.6%)\u003c/p\u003e\n \u003cp\u003e3 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; (6.5%)\u003c/p\u003e\n \u003cp\u003e2 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; (4.3%)\u003c/p\u003e\n \u003cp\u003e6 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; (13.0%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e30% \u0026nbsp; \u0026nbsp; \u0026nbsp; (21.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003eExtent of resection\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Biopsy \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Subtotal \u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Gross total\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; (6.5%)\u003c/p\u003e\n \u003cp\u003e18 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; (39.1%)\u003c/p\u003e\n \u003cp\u003e25 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; (54.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003e\u003csup\u003ea\u003c/sup\u003e\u003c/em\u003e\u003cem\u003eIQR, interquartile range; \u003csup\u003eb\u003c/sup\u003eECOG, Eastern Cooperative Oncology Group; \u003csup\u003ec\u003c/sup\u003eMGMT, O6-methylguanine-DNA methyltransferase.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eInfiltration patterns\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eAt diagnosis, tumours were localised to either the medial occipital lobe in 20 patients (43.5%) or the lateral occipital lobe in 26 patients (56.5%). Level 2 infiltration was present in 33 patients (71.7%) and level 3 in 27 patients (58.7%). In medial tumours, 15 patients (75%) had level 2 and 11 patients (55%) had level 3 infiltration. In lateral tumours, 18 patients (69.2%) had level 2 and 16 patients (61.5%) had level 3 infiltration. There was no statistically significant difference in the presence of level 2 or 3 infiltration between medial and lateral subsites (\u003cem\u003ep\u003c/em\u003e = 0.75 and \u003cem\u003ep\u003c/em\u003e = 0.76, respectively).\u003c/p\u003e\n\u003cp\u003eAmong those with level 3 infiltration, medial tumours involved the \u003cstrong\u003etrigone\u003c/strong\u003e in 7 patients (63.6%), \u003cstrong\u003esplenium\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003ein 4 patients (36.4%), and \u003cstrong\u003eanterior temporal lobe\u003c/strong\u003e in 1 patient (9.1%). In lateral tumours, the \u003cstrong\u003etrigone\u003c/strong\u003e was involved in 15 patients (93.8%), \u003cstrong\u003esplenium\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003ein 1 patient (6.3%), and \u003cstrong\u003eanterior temporal lobe\u003c/strong\u003e in 3 patients (18.8%). While trigone involvement appeared more frequent in lateral tumours and splenial involvement more common in medial tumours, none of these differences reached statistical significance (\u003cem\u003ep\u003c/em\u003e = 0.15 for trigone, \u003cem\u003ep\u003c/em\u003e = 0.15 for splenium and \u003cem\u003ep\u003c/em\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e= 0.62 for anterior temporal lobe). See \u003cem\u003eTable 2.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e2\u003c/strong\u003e Infiltration patterns, comparing medial and lateral (level 1) origin occipital lobe glioblastoma\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"633\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedial (n=20)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLateral (n=26)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal n\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003csup\u003ea\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003eLevel 2 infiltration\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e15 (75.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e18 (69.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e33 (71.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cem\u003e0.75\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003eLevel 3 infiltration\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e11 (55.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e16 (61.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e27 (58.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cem\u003e0.76\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 633px;\"\u003e\n \u003cp\u003e\u003cem\u003eLevel 3 subsite infiltration\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Trigone\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e7 (63.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e15 (93.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e22 (81.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cem\u003e0.15\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Splenium\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e4 (36.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e1 (6.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e5 (18.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cem\u003e0.15\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Anterior temporal lobe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e1 (9.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e3 (18.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e4 (14.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cem\u003e0.62\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003ea\u003c/sup\u003e p-values correspond to statistical comparisons of infiltration rates between medial and lateral tumour locations.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eRelapse patterns\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eRelapse occurred in 43 patients (93.5%), including 19 patients (95%) with medial tumours and 24 patients (92.3%) with lateral tumours. Of the relapsed patients, involvement in medial tumours included level 1 in 4 patients (21.1%), level 2 in 13 patients (68.4%), and level 3 in 18 patients (94.7%). Involvement in lateral tumours included level 1 in 8 patients (33.3%), level 2 in 20 patients (83.3%), and level 3 in 24 patients (100%).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOf the relapsed patients there was no statistically significant difference in involvement of level 3 at relapse based on initial tumour localization, 18 patients (94.7%) for medial tumours and 24 (100%) patients for lateral tumours, with a \u003cem\u003ep\u003c/em\u003e value of 0.44, respectively. At specific level 3 subsites, medial tumours involved the trigone in 10 patients (52.6%), the splenium in 9 patients (47.3%), and the anterior temporal lobe in 3 patients (15.8%). Lateral tumours involved the trigone in 18 patients (75%), the splenium in 4 patients (16.7%), and the anterior temporal lobe in 12 patients (50%). These differences were statistically significant for splenium (\u003cem\u003ep\u003c/em\u003e = 0.046) and anterior temporal lobe (\u003cem\u003ep\u003c/em\u003e = 0.026), but not for trigone (p = 0.198). See \u003cem\u003eTable 3, and Figure 2\u0026nbsp;\u003c/em\u003ewhich compares level 3 site specific relapse based on origin\u003cem\u003e. \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e3\u003c/strong\u003e Relapse patterns, comparing medial and lateral (level 1) origin occipital lobe glioblastoma\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"633\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedial (n=19)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLateral (n=24)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal n\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003csup\u003ea\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003eLevel 1 involvement\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e4 (21.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e8 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e12 (27.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003eLevel 2 involvement\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e13 (68.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e20 (83.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e33 (76.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cem\u003e0.295\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003eLevel 3 involvement\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e18 (94.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e24 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e42 (97.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cem\u003e0.440\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 633px;\"\u003e\n \u003cp\u003e\u003cem\u003eLevel 3 subsite infiltration\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003eTrigone\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e10 (52.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e18 (75%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e28 (66.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cem\u003e0.198\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003eSplenium\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e9 (47.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e4 (16.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e13 (31.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cem\u003e0.046\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003eAnterior temporal lobe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e3 (15.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e12 (50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e15 (35.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cem\u003e0.026\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003ea\u003c/sup\u003ep-values correspond to statistical comparisons of relapse site involvement based on medial and lateral tumour origin.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eAssociation of occipital lobe subsite with survival outcome\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSurvival outcomes in relation to tumour localization were not statistically significant.\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMedian OS was 16.3 months (95% CI: 13.1\u0026ndash;24.0) for medial tumours; and 18.0 months (95% CI: 15.1\u0026ndash;23.6) for lateral tumours, with a hazard ratio (HR) of 0.95 (95% CI: 0.51\u0026ndash;1.77; p = 0.876). Median RFS was 10.4 months (95% CI: 8.9\u0026ndash;14.3) for medial tumours and 9.3 months (95% CI: 7.7\u0026ndash;17.9) for lateral tumours, with an HR of 0.95 (95% CI: 0.52\u0026ndash;1.75; p = 0.869; log-rank p = 0.87).\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eOther factors and interaction with survival outcome\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eHigher ECOG scores at diagnosis tended to be associated with worse OS: 19.4 months for ECOG 0 (95% CI: 12.9\u0026ndash;26.0), 17.1 months for ECOG 1 (95% CI: 14.7\u0026ndash;19.6), and 11.4 months for ECOG 2 (95% CI: 11.0\u0026ndash;11.7). Incremental increases in ECOG were confirmed to be statistically significant in terms of association with worse OS (HR: 1.72; 95% CI: 1.14\u0026ndash;2.58; \u003cem\u003ep\u003c/em\u003e = 0.010). \u003cstrong\u003eAlthough not statistically significant, relapse-free survival (RFS) also tended to decline with increasing ECOG scores\u003c/strong\u003e. \u003cstrong\u003eEach one-point increase in ECOG was associated with a non-significant increase in relapse risk\u003c/strong\u003e (HR: 1.43; 95% CI: 0.96\u0026ndash;2.13; p = 0.082).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMGMT promoter methylation status\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003ewas available for 31 patients: 16 (51.6%) were unmethylated and 15 (48.4%) methylated. Median OS was longer in the methylated group at 23.6 months (95% CI: 15.7\u0026ndash;31.6) compared to 14.3 months (95% CI: 10.8\u0026ndash;17.7) in the unmethylated group.\u003cstrong\u003e\u0026nbsp;\u003cstrong\u003eMethylation was associated with statistically significant improved OS\u0026nbsp;\u003c/strong\u003e\u003c/strong\u003e(HR: 0.29; 95% CI: 0.12\u0026ndash;0.69; \u003cem\u003ep\u003c/em\u003e = 0.005). RFS was also longer in the methylated group, with a median of 17.9 months (95% CI: 8.0\u0026ndash;27.8) versus 8.7 months (95% CI: 7.5\u0026ndash;9.9) in the unmethylated\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003egroup.\u003cstrong\u003e\u0026nbsp;\u003cstrong\u003eThe risk of relapse was likewise improved and statistically significant in methylated tumours\u003c/strong\u003e\u0026nbsp;\u003c/strong\u003e(HR: 0.18; 95% CI: 0.07\u0026ndash;0.47; \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001).\u003c/p\u003e\n\u003cp\u003eHigher Ki-67 expression was associated with poorer outcomes. Every 10% increase in Ki-67 corresponded to statistically significant shorter median OS (HR: 1.58; 95% CI: 1.28\u0026ndash;1.96; p \u0026lt; 0.001) and shorter RFS (HR: 1.43; 95% CI: 1.17\u0026ndash;1.76; p \u0026lt; 0.001).\u003c/p\u003e\n\u003cp\u003eIn regards to extent of surgical resection, there was no association with either overall or relapse-free survival. OS was 15.7 months (95% CI: 6.3\u0026ndash;25.2) for biopsy, 15.5 months (95% CI: 8.3\u0026ndash;22.6) for subtotal resection, and 18.1 months (95% CI: 14.0\u0026ndash;22.3) for gross total resection. There was no statistically significant difference in OS when biopsy was compared to subtotal resection (HR: 0.72; 95% CI: 0.21\u0026ndash;2.47; p = 0.597) or gross total resection (HR: 0.58; 95% CI: 0.17\u0026ndash;1.95; p = 0.376). Median RFS was 13.1 months (95% CI: 4.1\u0026ndash;22.1) for biopsy, 10.2 months (95% CI: 9.3\u0026ndash;11.2) for subtotal resection, and 8.9 months (95% CI: 5.9\u0026ndash;11.8) for gross total resection. As with OS, there was no statistically significant difference in RFS when comparing subtotal resection (HR: 1.03; 95% CI: 0.30\u0026ndash;3.52; p = 0.966) or gross total resection (HR: 0.80; 95% CI: 0.23\u0026ndash;2.73; p = 0.721) to biopsy.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study provides a focused analysis of occipital lobe glioblastoma, a relatively uncommon tumour location[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], and examines the patterns of initial infiltration, relapse, and survival outcomes according to tumour subsite within the occipital lobe.\u003c/p\u003e\u003cp\u003eAlthough the patient sample population is small in numbers there was a reasonable distribution of medial (20 patients) and lateral (26 patients) occipital tumours. Tumour infiltration at diagnosis was common beyond the occipital lobe in both medial and lateral occipital subsites. With over 70% of patients demonstrating level 2 infiltration and 58.7% exhibiting level 3 infiltration.\u003c/p\u003e\u003cp\u003eInterestingly, analysis of relapse patterns suggested that progression in this cohort of occipital glioblastoma most frequently occurred at distant sites. High rates of recurrence were observed at level 2 and particularly at level 3, regardless of whether the tumour originated at a medial or lateral subsite within the occipital lobe. Only 21.1% of medial and 33.3% of lateral tumours relapsed at level 1. In contrast, level 2 involvement at relapse was seen in over two-thirds (68.4%) of medial tumours and 83.3% of lateral tumours, while level 3 involvement occurred in nearly all cases (94.7% and 100%, respectively). Indicating that within this cohort local or marginal tumour relapse was relatively uncommon. Additionally, there was no statistically significant difference in survival outcomes for the extent of surgery, thus suggesting the high risk of distant infiltration is more prominent than local disease. It may support the hypothesis that relapse occurs in predictable pathways rather than isotropic extension from the original contrast enhancing mass.\u003c/p\u003e\u003cp\u003eBetween occipital subsites there were statistically significant differences in relapse patterns, involving specific level 3 subsites. Medial tumours relapsed more frequently in the splenium and less frequently in the anterior temporal lobe compared to lateral tumours. Although not statistically significant, trigone involvement seemed to be more prominent amongst lateral tumours (75% vs 52.6%). Although the findings on analysis of infiltration were not statistically significant, they correlated with relapse patterns where splenium involvement appeared more common in medial tumours and trigone involvement more common in lateral tumours. These findings imply potential subsite-specific routes of tumour progression and may reflect differences in white matter connectivity or patterns. Medially the major white matter tracts such as cingulum and corpus callosum emerge from this region and thus extend into splenium. Laterally the inferior longitudinal fasciculus extends towards the trigone and anterior temporal lobe. See Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e for radiological examples.\u003c/p\u003e\u003cp\u003eThe OS of 17.4 months and RFS of 10.1 months are in keeping with reported survival outcomes for glioblastoma [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. This suggests that occipital localization of glioblastoma may not have a substantially different prognosis compared to tumours in other brain regions. Despite the anatomical distinctions in relapse patterns mentioned above, no statistically significant survival difference between medial and lateral occipital tumours was demonstrated.\u003c/p\u003e\u003cp\u003eThe limitations of this study include its retrospective design and undoubtedly its relatively small sample size. Additionally, subgroup analysis was somewhat incomplete, certain variables such as MGMT promoter methylation status for instance were not available for all patients. Furthermore given the somewhat rarity of occipital lobe glioblastoma comparative literature is limited, which restricts broader contextualisation of our findings.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study contributes valuable insight into the behaviour of occipital lobe glioblastoma. The high frequency of level 3 progression involving deep structures such as the trigone, splenium and anterior temporal lobe suggest that traditional isotropic margin expansion in radiotherapy based solely on the initial tumour location may underestimate the true extent of disease. This underscores the importance of further investigating the incorporation of likely pathways of spread, particularly white matter tracts, into radiotherapy planning.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003ch2\u003eCompeting Interests:\u003c/h2\u003e\u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003ch2\u003eEthics approval:\u003c/h2\u003e\u003cp\u003e This study was performed in line with the principles of the Declaration of Helsinki.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003ch2\u003eConsent to participate:\u003c/h2\u003e\u003cp\u003e Informed consent was obtained from all individual participants included in the study.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConsent to publish:\u003c/strong\u003e\u003cp\u003eThe authors affirm that human research participants provided informed consent for publication of de-identified data.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e\u003cp\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eM.S. developed the manuscript, contributed to data collection, performed statistical analyses, and contributed to data interpretation. C.K.L. contributed to statistical analyses, contributed to data interpretation, and reviewed the manuscript. M.B. conceived and designed the study, contributed to data collection and neuroanatomical site characterisation, and provided manuscript commentary and critical revision. All authors reviewed and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSalvalaggio A, Pini L, Bertoldo A, Corbetta M (2024) Glioblastoma and brain connectivity: the need for a paradigm shift. Lancet Neurol 23(7):740\u0026ndash;748\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eVan Den Bent MJ, Geurts M, French PJ, Smits M, Capper D, Bromberg JEC et al (2023) Primary brain tumours in adults. Lancet 402(10412):1564\u0026ndash;1579\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eStupp R, Hegi ME, Mason WP (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10:459\u0026ndash;466\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChinot OL, De La Motte Rouge T, Moore N, Zeaiter A, Das A, Phillips H et al (2011) AVAglio: Phase 3 trial of bevacizumab plus temozolomide and radiotherapy in newly diagnosed glioblastoma multiforme. Adv Therapy 28(4):334\u0026ndash;340\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA et al (2014) A Randomized Trial of Bevacizumab for Newly Diagnosed Glioblastoma. N Engl J Med 370(8):699\u0026ndash;708\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWeller M, Yung WKA (2013) Angiogenesis inhibition for glioblastoma at the edge: beyond AVAGlio and RTOG 0825. Neurooncology 15(8):971\u0026ndash;971\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eStupp R, Hegi ME, Gorlia T, Erridge SC, Perry J, Hong YK et al (2014) Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071\u0026thinsp;\u0026ndash;\u0026thinsp;22072 study): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol 15(10):1100\u0026ndash;1108\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNiyazi M, Andratschke N, Bendszus M, Chalmers AJ, Erridge SC, Galldiks N et al (2023) ESTRO-EANO guideline on target delineation and radiotherapy details for glioblastoma. Radiother Oncol 184:109663\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eStupp R, Weller M, Belanger K, Bogdahn U, Ludwin SK, Lacombe D et al (2005) Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma. N Engl J Med 352(10):987\u0026ndash;996\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHochberg FH, Pruitt A (1980) Assumptions in the radiotherapy of glioblastoma. Neurology 30(9):907\u0026ndash;907\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBurger PC, Heinz ER, Shibata T, Kleihues P (1988) Topographic anatomy and CT correlations in the untreated glioblastoma multiforme. J Neurosurg 68(5):698\u0026ndash;704\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGebhardt BJ, Dobelbower MC, Ennis WH, Bag AK, Markert JM, Fiveash JB (2014) Patterns of failure for glioblastoma multiforme following limited-margin radiation and concurrent temozolomide. Radiat Oncol 9(1):130\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHenssen D, Meijer F, Verburg FA, Smits M (2023) Challenges and opportunities for advanced neuroimaging of glioblastoma. Br J Radiol 96(1141):20211232\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLarjavaara S, M\u0026auml;ntyl\u0026auml; R, Salminen T, Haapasalo H, Raitanen J, J\u0026auml;\u0026auml;skel\u0026auml;inen J et al (2007) Incidence of gliomas by anatomic location. Neurooncology 9(3):319\u0026ndash;325\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eStatements \u0026amp; Declarations\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Glioblastoma, Occipital lobe, Radiotherapy, Infiltration patterns, Relapse patterns","lastPublishedDoi":"10.21203/rs.3.rs-8277737/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8277737/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose:\u003c/strong\u003e \u003cbr\u003e\n Target volume delineation protocols for glioblastoma utilise uniform or isotropic expansion around the surgical cavity and residual tumour, without considering specific sites at risk for infiltration. Tumours arising in different neuroanatomical sites may have specific pathways for infiltration. This study aims to review the infiltration and relapse sites for the occipital lobe glioblastoma to determine sites at risk, and potentially improve future target volume delineation protocols.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethod:\u003c/strong\u003e \u003cbr\u003e\n Patients with occipital lobe glioblastoma and managed with EORTC-NCIC Protocol were identified through a prospective database. Based on MRI analysis a qualitative description of sites of tumour infiltration and subsequent relapse was performed.\u003c/p\u003e\n\u003cp\u003eThese were categorized into neuroanatomical subsites adjacent to the occipital lobe: Level 1 related to origin gyrus; Level 2 adjacent gyral subsites; Level 3 subsites involved distant regions. These spatial patterns were assessed in relation to three major white matter tracts: inferior longitudinal fasciculus, cingulum, and corpus callosum.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e \u003cbr\u003e\n 46 patients were analysed. At diagnosis, 20 patients (43.5%) had medial occipital lobe involvement and 26 (56.5%) had lateral involvement. Level 2 and level 3 infiltration were observed in 33 (71.7%) and 27 (58.7%) of patients.\u003c/p\u003e\n\u003cp\u003eRelapse occurred in 43 patients (93.5%), 28% at level 1, 77% at level 2, and 98% at level 3. Level 3 relapse sites included the trigone (70%), splenium (30%), and anterior temporal lobe (35%). Lateral tumours relapsed more commonly in the trigone (75% vs 52.6%) and anterior temporal lobe (50% vs 15.8%, \u003cem\u003ep\u003c/em\u003e=0.026), while medial tumours more frequently involved the splenium (47.3% vs 16.7%, \u003cem\u003ep\u003c/em\u003e=0.046).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e \u0026nbsp;\u003cbr\u003e\n Infiltration and relapse of glioblastoma involving the occipital lobe suggests distinct neuroanatomical patterns which may guide radiation therapy target volume delineation.\u003c/p\u003e","manuscriptTitle":"Assessment of patterns of infiltration and relapse of patients with glioblastoma of the occipital lobe","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-11 00:47:35","doi":"10.21203/rs.3.rs-8277737/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b6e3f154-95b9-44c5-bd0b-5e448b87571e","owner":[],"postedDate":"December 11th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-12-22T12:53:44+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-11 00:47:35","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8277737","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8277737","identity":"rs-8277737","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}