PURPOSE:Based on bioeffect modeling of published outcomes after radiation therapy for head and neck squamous cell carcinoma with various time-dose-fractionation, we hypothesized that a 20-fraction hypofractionated (HFX) schedule delivering 55 Gy in 20 fractions, 5 fractions per week, over 4 weeks would be noninferior to a 33-fraction accelerated, normofractionated (NFX) 2 Gy per fraction schedule, delivering 66 Gy in 2-Gy fractions, 6 fractions per week over 5.5 weeks with respect to both local tumor control and late adverse events. METHODS AND MATERIALS:The HYPNO (HYPo-fractionated vs NOrmo-fractionated radiation therapy for head and neck squamous cell carcinoma) trial was designed as a multicenter, pragmatic, embedded, 2-arm, unblinded, randomized controlled noninferiority trial with dual primary endpoints, loco-regional tumor control, and grade 3 or higher late adverse events with a 10% noninferiority margin for both endpoints. The trial was open for enrollment in 12 centers, each adhering to their standard of care to the extent that it was consistent with the requirements of the trial protocol. Concurrent chemoradiation therapy with 35 mg/m2 cisplatin weekly was permitted. RESULTS:Between March 2014 and February 2020, 792 patients were centrally randomized: 395 to HFX and 397 to NFX. Accrual closed, with all outcome data still blinded, with 792 of a planned 836 patients (94.7%) enrolled, in part due to the emerging COVID-19 pandemic. The HYPNO test arm passed the separate noninferiority tests for both loco-regional tumor control (P = .04) and grade 3+ late adverse events (P = .004). At 3 years, the absolute difference in outcome between the 2 arms was ≤1.4 percentage points for overall survival, progression-free survival, loco-regional control, and grade 3+ late adverse events. The planned subgroup analyses showed no statistically significant heterogeneity of effect estimates for loco-regional control between the 2 trial arms. CONCLUSIONS:The HYPNO test arm schedule was shown to be noninferior with respect to both loco-regional tumor control and grade 3+ late adverse events.

Background and purposeInterpretation of imaging findings after radiation can be challenging in patients with high-grade glioma. Appearance of contrast-enhancing lesions during follow-up imaging poses difficulty in differentiating true progression from treatment-related changes. In the current study, we report patterns and clinical outcomes of radiation-induced subependymal enhancement.Materials and methodsPatients with histopathological diagnosis of HGG developing radiation-induced contrast enhancement in the subependymal region were considered in the retrospective study. The subependymal enhancement was required to be in the high-dose region of radiotherapy. Patients underwent multiparametric magnetic resonance imaging (MRI), which included T1-contrast, T2-weighted, perfusion, and spectroscopy. Confirmation of radiation changes rather than disease progression was decided based on regression or stability of concerned findings on follow-up imaging.ResultsThirty-four patients were included in the analysis. The median time from radiotherapy to onset of subependymal enhancement was 15 months. The enhancement pattern was feathery, nodular, and linear in 53%, 35%, and 3% of patients, respectively. A T2-hyperintense signal with a hypointense rim was seen in 74% of patients. Majority of these lesions were isoperfused (26%) or hypoperfused (47%). The median radiological follow-up after onset of subependymal enhancement was 7 months (range 1-61 months). At final follow-up, complete resolution, partial regression, and stable findings of the concerned enhancement were seen in 18%, 38%, and 44%, respectively.ConclusionSubependymal enhancement can be seen following radiation, which should be considered during the evaluation of follow-up imaging. Multiparametric MRI with specific contrast patterns, T2-weighted findings, and perfusion imaging can help identify radiation-induced enhancement.

TPS2104 Background: Both Temozolomide (TMZ) and PCV are standard adjuvant chemotherapy regimens used in treatment of grade 2 gliomas with high risk features and grade 3 gliomas. The PCV regimen has a complex schedule, higher rate of adverse events (esp myelosuppression), and is difficult to administer, but has long-term data with an overall survival benefit. On the other hand,TMZ is an oral drug, with a simple dosing schedule, and fewer adverse events. Currently, there is lack of data directly comparing PCV to TMZ, there is emerging evidence to suggest that PCV may be the regimen of choice for oligodendrogliomas (ODGs). There is often debate on the choice of adjuvant chemotherapy. Hence we are conducting this study to compare TMZ with PCV in this setting. Methods: This is an ongoing phase 3, parallel-arm, non-inferiority trial. Adults with high-risk grade 2 (age ≥40 years and/or the presence of residual disease ≥1 cm after maximal safe resection) or grade 3 gliomas, are randomized 2:1 to receive TMZ or PCV after adjuvant radiation (RT). Patients receive adjuvant focal conformal radiation, with doses between 54 to 59.4 Gy at 1.8-2 Gy/fraction with conventional fractionation. In the TMZ arm, patients receive RT with concurrent TMZ 75 mg/m 2 /day (max. 49 days) followed by adjuvant TMZ 150-200 mg/m 2 for 5 of 28 days (max. 12 cycles). In the PCV arm, patients receive Procarbazine 60 mg/m 2 on days 8-21, CCNU 110 mg/m 2 on day 1 and Vincristine 1.4 mg/m 2 on days 8, 29 of a 56-day cycle (maximum 6 cycles). Adjuvant chemotherapy is started within 8 weeks of completing RT. Adverse events are recorded as per CTCAE v4.03. EORTC QLQ C-30 & QLQ BN-20 is used for quality of life (QoL) assessment. Follow up evaluation will be conducted every 3 months in the 1 st year, every 4 months in the 2 nd year, and every 6 months from the 3 rd to 5 th year, then annually. The primary endpoint of the study is Progression-Free Survival (PFS). Secondary endpoints are Overall Survival (OS), safety,compliance & QoL. Sample Size: Assuming a 3-year PFS of 70% in the PCV arm, with type 1 error of 5% (1- sided), type 2 error of 20%, with 2:1 ratio of accrual (in favor of the TMZ arm) for 10 years, with a study duration of 15 years, to show a non-inferiority by 12% for the upper limit of 95% confidence interval of the PFS with one interim analysis; the sample size estimated by group sequential design for time-to-event outcome was 216. Statistical analysis: Kaplan Meir analysis will be used to estimate the PFS & OS and log rank test will be used for comparison between two arms.Cox proportional hazard model will be constructed for calculation of hazard ratio with its 95%CI. An interim analysis will be performed at 82 events of progression. If the log rank p value for the difference in the estimated PFS of the 2 arms is ≤ 0.006 then the trial will be terminated. Otherwise the trial will continue and undergo a final analysis at 163 events of progression. Clinical trial information: CTRI/2018/07/015056.

6000 Background: The role of adjuvant radiotherapy (RT) in early-stage, node-negative oral squamous cell carcinoma (OSCC) with one or more intermediate risk factors - such as depth of invasion (DOI) ≥5 to ≤10mm, perineural invasion (PNI), lymphovascular emboli (LVE), or poor differentiation - remains debatable and is largely based on retrospective data. This multicenter, open-label, phase III randomized controlled trial was designed to assess the impact of post-operative adjuvant RT in this setting. Methods: Patients with early-stage (pT1-T2), node-negative (pN0) OSCC undergoing adequate surgery (defined as clear margins ≥5mm and at least ipsilateral level I-III neck dissection with ≥16 nodes) with presence of one or more intermediate risk factors were screened. Eligible patients underwent stratified randomization (oral cavity subsite, PNI/LVE, and differentiation) in 1:1 ratio to either observation or adjuvant RT (60Gy in 30 fractions over 6-weeks) to the resected tumor-bed and at-risk neck nodal region after written informed consent. Primary endpoint was loco-regional recurrence-free survival (LRFS) measured from randomization to first documented event of local and/or regional recurrence from index cancer. All time-to-event outcomes were computed using Kaplan-Meier (KM) method with log-rank test for comparison and expressed as 3-year point estimates with 95% confidence intervals (CI). The planned sample size (N=392) provided 80% power at an α of 0.05 to detect a Hazard Ratio (HR) of 0.6256, assuming 3-year LRFS of 70% in the observation arm. Results: Following curative surgery, a total of 392 patients were randomized (191 to adjuvant RT; 201 to observation). Baseline characteristics were balanced between the two arms. At a median follow-up of 47.2 months (inter-quartile range=30-59.4 months), 3-year KM estimate of LRFS was 89.2% in adjuvant RT arm vs 80.9% in observation arm (HR=0.52, 95%CI=0.30-0.91; p=0.02) in the intention-to-treat (ITT) population and 91.1% vs 80.9% (HR=0.43, 95%CI=0.23-0.80; p=0.01) on per-protocol (PP) analyses. Cumulative incidence of loco-regional failure with death as competing event was 10.6% (95%CI=6.1%-15.1%) with adjuvant RT and 18.9% (95%CI=13.3%-24.6%) with observation (HR=0.52, 95%CI=0.30-0.91; p=0.021) in the ITT population and 8.7% (95%CI=4.3%-13.1%) vs 18.9% (95%CI=13.3%-24.6%) (HR=0.43, 95%CI=0.23-0.79; p=0.007) on PP analyses. Disease-free and overall survival were not significantly different between the two arms. Subgroup analysis identified oral tongue deriving higher benefit of adjuvant RT compared to buccal mucosa. Conclusions: Adjuvant RT significantly reduces risk of loco-regional recurrence for early-stage, node-negative adequately resected OSCC, particularly oral tongue. However, such reduction in loco-regional failure does not translate into significant survival benefit. Clinical trial information: CTRI/2017/07/009114.

ABSTRACT Background: Procarbazine, lomustine, vincristine (PCV) and temozolomide (TMZ) are adjuvant therapy options for grade 2 and 3 gliomas. We report compliance, toxicity, and quality of life (QoL) outcomes from an ongoing study comparing these regimens. Objectives: The primary objective was to determine whether adjuvant TMZ is noninferior to PCV in terms of progression-free survival. Secondary objectives were to compare compliance, toxicity, and QoL between the two regimens. Materials and Methods: Adults with high-risk grade 2 or 3 gliomas were randomized (2:1) to receive TMZ or PCV after radiotherapy. The TMZ arm received concurrent TMZ (75 mg/m 2 /day) followed by adjuvant TMZ (150-200 mg/m 2 , days 1-5 every 28 days, up to 12 cycles). The PCV arm received procarbazine (60 mg/m 2 , days 8-21), lomustine (110 mg/m 2 , day 1), and vincristine (1.4 mg/m 2 , days 8 and 29) every 56 days for up to 6 cycles. Results: This analysis included the first 50 patients (TMZ, n = 32; PCV, n = 18). Two patients in each arm did not initiate adjuvant chemotherapy. Chemotherapy completion rates were higher with TMZ (86.7%, n = 26) than PCV (68.8%, n = 11). Dose reductions were significantly more frequent with PCV (68.8%, n = 11 vs 3.3%, n = 1; P < 0.001). Grade ≥3 anemia ( P , 0.011), neutropenia ( P , 0.001), thrombocytopenia ( P , 0.015), and lymphopenia ( P < 0.001) were significantly higher with PCV. QoL did not differ significantly between arms. Conclusion: Adjuvant PCV is feasible with careful monitoring, although it is associated with higher toxicity than TMZ.

Abstract Background Optic pathway/hypothalamic gliomas (OPHG) comprise approximately 15% of low-grade gliomas. Despite favorable overall survival, these tumors are associated with significant visual and endocrine morbidity. Surgical resection is often limited by location, and radiotherapy (RT) carries substantial long-term toxicity. Methodology Children ≤18 years diagnosed with OPHG between January 2011 and December 2022 were included. Chemotherapy was used as the initial treatment strategy, with vincristine–carboplatin as first line,vinblastine monotherapy in neurofibromatosis (NF)-associated tumors and trametinib in recent years. RT was avoided or delayed and generally administered after failure of two systemic therapy lines or symptomatic progression. Baseline and serial visual and endocrine assessments were performed. Progression-free survival (PFS), radiation-free survival (RaFS), and overall survival (OS) were estimated using Kaplan–Meier methods. Results A total of 142 children were included; median diagnosis age 77 months, 73 (51.4%) male. Tumor location was hypothalamic in 122 (87.1%), optic nerve plus chiasma in 13 (9.3%), and optic nerve alone in 5 (3.6%). Presenting features included visual symptoms (78.2%), raised intracranial pressure (40.8%), diencephalic syndrome (7%), precocious puberty (11.3%), seizures (9.2%), and hemiparesis (4.2%). Thirty-four patients (24%) had NF. Among those tested, BRAF alterations included BRAFV600E mutation (0.5%) and fusion (40%). Three patients were observed; 139 received first-line therapy, 48 second-line, 10 third-line, and 3 fourth-line treatment. Overall, 46 (32.4%) received RT. At a median follow-up of 68months, 5-year PFS was 61.2±4.7% RaFS76.2±4%and OS 87.7±2.5%. At last follow-up, 3.5% were blind, 57% had poor vision, and 45.8% had endocrine dysfunction. Irradiated children had a higher endocrine morbidity (51% vs 22%, p < 0.001), but no improvement in vision. Conclusions Although survival outcomes are favorable in OPHG, survivors experience a substantial burden of long-term effects related to tumor location and treatment. Early diagnosis, multidisciplinary management, and long-term rehabilitation are essential to optimize quality of life.

Abstract Background With excellent long-term survival, contemporary treatment of pediatric low-grade glioma (pLGG) focuses on minimizing late toxicities and improving quality of life. Neuroradiation is associated with significant long-term sequelae, particularly in younger children. We evaluated the feasibility of chemotherapy as a radiation-sparing or delaying strategy in pLGG. Material and Methods Children <18 years with radiologically or histologically confirmed pLGG treated between January 2011 and December 2022 were included. Management comprised surgery where feasible, observation following gross resection or favorable biology, and systemic therapy after multidisciplinary discussion ( vincristine–carboplatin first-line, vinblastine monotherapy second-line or in neurofibromatosis (NF)-pLGG, and trametinib in recent years). Radiotherapy (RT) was avoided or delayed whenever possible and generally administered after failure of two systemic lines or symptomatic progression. Progression-free survival (PFS), radiation-free survival (RaFS), and overall survival (OS) were estimated using Kaplan–Meier methods. Results In 423 patients, median age at diagnosis was 8 years; 10.6% had NF. Common sites included cerebellum (26%), optic pathway hypothalamic (33.5%), cerebral hemispheres (18.7%), and brainstem (6.4%). At a median follow-up of 70 months, 413 patients received first-line therapy; 139 second-line, 23 third-line and 5 fourth-line. 140 (31.7%) ultimately received RT; median age at RT was 11years, and median time to RT 24months. 6-year PFS was 61.9%, RaFS 70.2%, and OS 90.2%. RaFS was 72% in BRAF fusion (n = 77) and 43% in BRAF-v600E mutant (n = 31), p = 0.01, and median RaFS was 77months and 31months respectively. Patients with NF (n = 42) had higher PFS (83.2% vs 59.7%, p = 0.1). Endocrine dysfunction was more frequent after RT (21.6% vs 7.2%, p < 0.001). One patient each had high-grade transformation, Moya moya disease and cavernoma. Conclusion RT could be avoided in a substantial proportion of children, especially BRAF- fusion, and delayed in others, resulting in fewer late toxicities. A radiation-sparing approach is feasible across settings with careful multidisciplinary decision-making.

The role of adjuvant fractionated radiotherapy (aFRT) after gross total resection (GTR) of WHO-2 meningiomas remains unclear. We aimed to estimate the effect of aFRT on recurrence risk and survival following GTR and subtotal resection (STR). We analyzed 1452 patients with WHO-2 from our international, multicenter database (followed between 1989 and 2019). Outcomes were recurrence (10-year follow-up) and death (5-year follow-up). Risk estimates were obtained using competing risks and survival analysis. Average treatment effects were estimated by G-computation, adjusted for potential confounding by age, sex, Simpson grade, Ki-67 proliferation index, location, country group (universal healthcare or not), and year of treatment initiation. The robustness of findings was examined through sensitivity analyses. Overall, 276 of 1452 patients (19.0

Abstract Background TERT promoter(TERTp) mutation has become an emerging marker of the adult subtype of SHH-activated medulloblastoma(MB), which is associated with a better prognosis. The study aims to evaluate correlation of TERTp mutations with various clinical, histoarchitectural and molecular features in MB. Materials and Methods Histologically and molecularly diagnosed cases of MB by targeted gene expression profiling(GEP) between the years 2021-2024 were evaluated for TERTp mutation by Droplet digital PCR(DdPCR) Results In a cohort of 201 cases, age range were-0-3years: 32(15.9%), 4-6years: 47(23.4%), 7-18years: 85(42.3%), 19-25years: 17(8.4%), 26-39 years: 18(8.9%) and ≥40years: 2(1%).M:F ratio-2.0:1. The cases were molecularly grouped as WNT-activated(n = 35,17.4%), SHH-activated and TP53 wildtype immunophenotype(64,31.8%), SHH-activated and TP53 mutant immunophenotype(3,1.4%) and non-WNT/non-SHH group[99(49.2%)- 32(15.9%)group3, 55(27.3%)group4, 12(5.9%)unclassified]. Classic(n = 138,68.6%) histoarchitecture was the most common followed by D/N (n = 38,18.9%) ,LC/A(n = 15,7.5%), with myogenic differentiation(NOS; n = 6,2.9%) and MBEN(n = 4,2%) histoarchitecture.Overall frequency of TERTp mutation was 16.9% (n = 34). 29 were of C228T and 5 were of C250T type of mutations. TERTp mutations were significantly associated with adult age-group (≥19 years) and SHH-activated group(p < 0.001). The frequency of mutation was 6.1% (n = 10) and 70.3% (n = 29) in ≤ 18 years and >18 years respectively. Among mutant cases,30-SHH-activated cases, 2 non-WNT/non-SHH group, and 2 WNT-activated cases (p < 0.001). 14(8.6%) were midline and 20(54.1%) were laterally localized tumours.17 cases showed classic and 17 showed D/N histoarchitecture. None of the mutant cases showed TP53-mutant immunophenotype, monosomy 6, and MYCN amplification. The one-year OS for TERTp mutant cases was better than TERT promoter wild-type cases. Conclusion TERTp mutations were common(92.3%) in adult SHH-activated MB patients, observed across classic and D/N histoarchitectural patterns, predominantly in lateralized locations, absent in MYCN-amplified and TP53-mutated cases, and associated with better overall survival.

Abstract Purpose The Ki-67 proliferation index (Ki-67 PI) has been associated with meningioma recurrence, yet its clinical utility remains debated. Whether Ki-67 PI provides prognostic information across subgroups defined by both WHO grade and extent of resection remains to be investigated. Methods We analyzed 5,050 patients with intracranial meningiomas from the international PERNS cohort (42 centers, diagnosed between 1989–2019) who underwent surgical resection without postoperative radiotherapy. Ki-67 PI prognostic accuracy was assessed up to 10 years postoperatively by using ROC analyses and estimating its association with the risk of recurrence. Results Results demonstrated that the prognostic value of Ki-67 PI differed by subgroups defined by WHO grade and Simpson grade. For patients with the same Simpson grade (1–3), the predictive accuracy of Ki-67 PI for 10-year recurrence risk was stronger in WHO-2 than in WHO-1. Within WHO-1 and WHO-2 meningiomas, the predictive accuracy of Ki-67 PI increased with higher Simpson grade (1–3). However, no predictive value was observed in Simpson grade 4 resections regardless of WHO grade. Conclusion These findings highlight that Ki-67 PI should be interpreted in the context of both WHO grade and extent of resection, and, if done so, may offer potential value to refine individualized surveillance strategies in meningioma patients with gross total resection in the initial 10-year postoperative timeframe. Findings cannot be extrapolated beyond 10 years, which may be particularly relevant for WHO-1 tumors with low Ki-67 PI and Simpson grade 1 resection.

Purpose:H3K27M-altered diffuse midline glioma (DMG) is an aggressive pediatric-type high-grade glioma (HGG) arising from midline structures in the central nervous system. This report summarizes the experience with this disease entity at a tertiary-care comprehensive cancer center in a low-middle income country. Methods:Patients with biopsy-proven H3K27M-altered DMG were identified from prospective database with retrospective data extraction and analysis. Following biopsy/debulking surgery, patients were treated with radiotherapy (RT) with or without temozolomide (TMZ). Progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan-Meier methods and expressed as point estimates with 95% confidence intervals (CI). Results:A total of 225 patients with biopsy-proven H3K27M-altered DMG were identified; survival analysis was restricted to 194 patients with outcome data. Median age at diagnosis was 20 years with 70% patients being ≥12 years of age. At a median follow-up of 12 months, 1-year PFS and OS were 30.8% (95% CI: 24.8%-38%) and 46.8% (95% CI: 40%-54.5%), respectively, yielding median PFS and OS of 7 months (95% CI: 6-10 months) and 12 months (95% CI: 10-14 months), respectively. Leptomeningeal dissemination at initial diagnosis (10.9%) and on follow-up (24.5%) was documented in a substantial proportion of evaluable patients. Female gender, supratentorial location, debulking surgery, administration of RT, and addition of TMZ emerged as prognostic factors for survival. Conclusion:Despite contemporary standard-of-care chemoradiotherapy paradigm, prognosis of H3K27M-altered DMG-an aggressive pediatric-type HGG-remains universally poor with virtually no long-term survivors. Deeper molecular insights and better elucidation of biological underpinnings are required to guide discovery of novel targeted therapeutics.

Several clinical and genetic factors including single nucleotide polymorphisms (SNP) in the O6-methylguanine-DNA methyltransferase (MGMT) gene are associated with increased risk of temozolomide (TMZ) induced myelotoxicity. We have previously reported substantially higher frequency of variant T allele of L84F (SNP in MGMT gene) in Indian patients with clinically relevant myelotoxicity compared to normal South Asian population. We now report findings from our case-control study correlating clinical and genetic factors with TMZ-induced ≥grade 3 myelotoxicity in adult diffuse glioma. We enrolled 46 cases (≥ grade 3 myelotoxicity) and 50 controls (grade 0–1 myelotoxicity) in the present case-control study. Association of various clinical and genetic characteristics with TMZ-induced severe myelotoxicity was analysed using chi-square test and Fisher’s exact test as appropriate and expressed as odds ratio (OR) with 95

Haemangiopericytoma, now reclassified as solitary fibrous tumour, of the central nervous system (CNS), constitutes an exceedingly rare mesenchymal neoplasm originating from the pericytes of meningeal capillaries. These neoplasms typically exhibit a slow growth pattern, with the level of aggressiveness escalating in correlation with higher grades. Minor subsets of this population experience recurrence, and the optimal therapeutic strategy in such circumstances remains ambiguous. Therefore, there exists a continual opportunity for the introduction of innovative treatment modalities. Fibroblast Activation Protein is significantly overexpressed in these tumours, rendering it a promising target for both diagnostic purposes and radioisotope therapy (RIT). We present an unusual case of haemangiopericytoma of the CNS, classified as WHO Grade 3, which manifested recurrence following subtotal resection and adjuvant radiotherapy. The patient subsequently underwent two sessions of Lutetium-177 FAP 2286 (Lu177 FAP2286) radionuclide therapy and exhibited a remarkable response to the FAP-targeted treatment.

Recurrence risk estimates underpin meningioma research, including molecular classification and clinical trial benchmarking, yet are often based on retrospective or historical data. The aim of this study was to assess the variation of recurrence risk estimates across calendar periods, WHO classification editions, geographical settings, and healthcare systems.thetermine We analyzed 4,111 patients with primary WHO-1/-2 meningiomas from 31 centers in 15 countries (1990–2019). Recurrence was defined according to local radiological assessment. The 5- and 10-year recurrence risks were estimated using regression standardization with inverse probability of censoring weights, adjusting for key clinical, surgical, and histopathological variables. Recurrence risk estimates varied across all domains examined. More recent calendar periods were associated with higher predicted recurrence risk, particularly for WHO-2 at 5 years (e.g., ≥ 2013 vs. ≤ 2007: RR 1.60, 95

ABSTRACT Objectives HPV‐negative oropharyngeal squamous cell cancer (OPSCC) is associated with poor clinical outcomes. The main objective of this study was to evaluate prognostic factors of OPSCC treated with definitive chemoradiotherapy (CTRT). Materials and Methods Consecutive patients of OPSCC treated with definitive CTRT in a tertiary care center from January 2013 to December 2017 were analysed retrospectively. Kaplan–Meier method was used for survival analysis, Log‐rank test was used for univariate analysis (UVA), and Cox regression method was used for multivariate analysis (MVA). Results Out of 630 eligible patients, 543 (86.1%) had locally advanced stage according to AJCC 7th edition. HPV status was known for 500 patients, of which 55 (11%) tested p16 positive, reflecting a predominantly HPV‐negative cohort. Chemo‐radiotherapy was offered to 447 (71%) patients. Intensity‐modulated‐radiotherapy (IMRT) technique was used for 163 (25.9%) patients. On UVA KPS ≤ 80 (p = 0.001), p16 negative tumours (p < 0.001), T3‐T4 stage (p < 0.001), advanced group stage (AJCC 8th ed.) (p < 0.001), conventional RT technique (p < 0.001), RT dose < 66 Gy EQD2 (p < 0.001) and residual disease after treatment (p < 0.001) were associated with poor Locoregional control (LRC) rates. On MVA p16 negative tumours (HR 3.1 [95% CI 1.8–5.3]), T3‐T4 stage (HR 1.6 [95% CI 1.2–2.2]), conventional RT technique (HR 1.6 [95% CI 1.5–2.3]), RT dose < 66 Gy EQD2 (HR 2.2 [95% CI 1.5–3.4]) were independent prognostic factors for poor LRC. These variables were also significant for local control, disease‐free free and overall survival. Conclusion In this predominantly HPV‐negative OPSCC cohort, HPV status, T stage, RT technique, and RT doses > 66 Gy were independent prognostic factors for all outcomes.

Abstract Introduction Infantile central nervous system (CNS) tumours (≤3 years) are histomolecularly distinct from those in older children. Aim To characterize the histomolecular spectrum of infantile CNS tumours diagnosed at our institution over the past decade. Methods We retrospectively collated histopathological, immunohistochemical, molecular, and clinicoradiological data for all primary CNS tumours diagnosed in children ≤3 years (2015–2024). Integrated diagnoses followed the WHO Classification of CNS Tumours, 5th edition. Results The cohort comprised 464 cases (≤1 year: n = 41 [8.8%]; >1–3 years: n = 423 [91.2%]); median age 28.1 months (IQR 19.1–37.3); 306 males and 158 females. Tumour locations were posterior fossa (n = 269, 58%), cerebral hemispheres (n = 91, 19.6%), suprasellar region (n = 43, 9.3%), pineal (n = 16, 3.4%), lateral ventricles (19, 4.1%), thalamus (7, 1.5%), and spinal (19, 4.1%). Gliomas, glioneuronal, and neuronal tumours predominated (n = 218, 47.0%), including low-grade glial/glioneuronal (n = 95, 43.5%), high-grade glial (n = 27, 12.4%), astrocytic NOS (n = 3, 1.4%), and ependymal (n = 93, 42.7%). Embryonal tumours constituted 199 (42.9%): medulloblastoma (n = 115), atypical teratoid/rhabdoid tumour (n = 45), embryonal tumour with multilayered rosettes (n = 22), and CNS embryonal tumour, NOS (n = 17). Choroid plexus tumours (n = 23) and pineoblastomas (n = 13) were uncommon; adamantinomatous craniopharyngioma (n = 4), germ cell tumours (n = 5), and meningioma (n = 2) were rare. Pilocytic astrocytoma was the most common entity (n = 78, 16.8%). Among 49 pilocytic astrocytomas with molecular data, BRAF alterations were detected in 31 (KIAA1549-BRAF fusions: 28; BRAFV600E: 3); 18 were negative. Ependymomas included posterior fossa group A (PF-A) as the most frequent subtype (40/69 posterior fossa) and supratentorial ependymoma, ZFTA-altered (12/24 supratentorial). Among medulloblastomas, SHH-activated/TP53-wildtype was most common (n = 42), followed by non-WNT/SHH Group 3 (n = 33). Conclusion In infants, gliomas/glioneuronal/neuronal tumours are the predominant WHO CNS5 family, with medulloblastomas the most frequent group overall; however, pilocytic astrocytoma is the single most common specific diagnosis. These data underscore age-specific histomolecular patterns with implications for diagnosis and targeted management.

Abstract Background Radiotherapy plays an integral role in the management of several pediatric brain tumors, improving survival. Neurocognitive function can be affected by radiotherapy in survivors, which is often multifactorial, including primary disease as well as other treatment modalities contributing to decline. We present real-world data of neurocognitive function of a large cohort of pediatric patients treated with radiotherapy. Methods The retrospective study included patients aged < 18 years treated with conformal radiotherapy, and neurocognitive evaluation was done before starting radiation, with a proportion of patients having follow-up evaluation. Patients were treated with image-guided photon radiotherapy between 2010 and 2023. Neurocognitive evaluation was done using the age-appropriate Wechsler Intelligence Scale for Children (WISC). Whenever feasible, follow up evaluation was done on an annual basis post-radiotherapy. Results Pre-radiotherapy evaluation was available in 289 patients with common histologies being medulloblastoma (73), posterior fossa ependymoma (65), craniopharyngioma (65), optic pathway glioma (42), and germ cell tumor (22). Supratentorial location was seen in 59%, and low-grade or benign histology in 57% of patients. Deficits in Full Scale Intelligence Quotient (FSIQ) were seen in 32%, with supratentorial tumors and midline location serving as independent risk factors. The median FSIQ was 86 (IQR 73-101), and domains in Performance Quotient were more affected than Verbal Quotient. Two-year follow-up was available in 85 patients with a median FSIQ of 87 (IQR 76-102). Five-year post-radiotherapy median FSIQ was 91 (IQR 71-104) as available from 51 patients. Conclusion One third of patients had pre-radiation deficits, with disease location serving as a major risk factor. Conformal image-guided photon radiotherapy led to preservation of neurocognition in patients, with modern techniques like proton beam therapy offering further scope of improving neurocognitive function.

Craniospinal irradiation (CSI) forms an integral role in the management of primary brain tumors like embryonal tumors (medulloblastoma), non-seminomatous germ cell tumors, metastatic ependymoma, etc. The cranial component with radiation of whole brain and boost can lead to decline in neurocognitive function. Memantine is an NMDA receptor antagonist with an established role in reducing radiation-induced neurocognitive decline in patients treated with whole brain radiotherapy, but the benefit in pediatric and adults treated with CSI remains unclear. This is a phase 3 open-label, randomized controlled trial. Pediatric and young adults (5 to 39 years) treated with CSI will be eligible for the study. Patients will be randomized in 1: 1 accounting for stratification factors such as age, CSI dose, location of tumor boost, and use of chemotherapy. Patients in the experimental arm will receive memantine 5 mg once daily for 1 week, 5 mg twice daily for 1 week, and finally escalated to 10 mg twice daily for 6 months. The primary endpoint will be cognitive deterioration-free survival (CDFS) at 2 years, with secondary endpoints being safety and compliance of memantine, slope of decline of neurocognitive scores, and survival. To demonstrate the improvement of 2-year CDFS of 75