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Central nervous system (CNS) tumors are the second most common cause of cancer in children when incidence rates of cancer are estimated according to the Indian population dynamics based on 2011 consensus. As per the estimates, CNS tumors account for 20.1% of cancer burden in children aged between 0 and 14 years and 16.8% when 0 to 19 years age group is considered. The most common pediatric brain tumors are astrocytoma and medulloblastoma followed by other embryonal tumors, craniopharyngioma, and ependymal tumors. The incidence of CNS tumors in children from India is similar to the western high-income countries, other than slightly higher incidence of craniopharyngioma in Indian children.

Tamoxifen is a selective estrogen receptor modulator and forms the mainstay of endocrine therapy in premenopausal women with breast cancer in both adjuvant and metastatic setting. Common adverse effects are menopausal symptoms with venous thrombosis and endometrial carcinoma being rarer but more sinister complications. Vasculitis is a rarely reported reaction to tamoxifen. We report a case of a 38-year-old woman with locally advanced breast cancer, who received neoadjuvant chemotherapy followed by modified radical mastectomy and adjuvant paclitaxel. She was on maintenance tamoxifen and leuprolide for 3 months, when she presented with pruritic bilateral maculopapular rash over all her limbs, legs more than hands. A skin biopsy from the left lower limb confirmed the diagnosis of vasculitis. Tamoxifen was stopped, and patient was switched to letrozole and leuprolide. She was given antihistamines, antibiotics, fusidic acid, vitamin C, and topical steroids. The lesions resolved completely in 1 month after stoppage of tamoxifen. We report this rare side effect of tamoxifen so that oncologists can effectively diagnose and treat this distressing but reversible condition.

Background: Re-irradiation (ReRT) is an effective treatment modality in appropriately selected patients with recurrent/progressive high-grade glioma (HGG). The literature is limited regarding recurrence patterns following ReRT, which was investigated in the current study. Methods: Patients with available radiation (RT) contours, dosimetry, and imaging-based evidence of recurrence were included in the retrospective study. All patients were treated with fractionated focal conformal RT. Recurrence was detected on imaging with magnetic resonance imaging (MRI) and/ or amino-acid positron emission tomography (PET), which was co-registered with the RT planning dataset. Failure patterns were classified as central, marginal, and distant if >80%, 20–80%, or

There is lack of consensus regarding optimal adjuvant therapy in elderly glioblastoma (GBM). We have been treating elderly (≥60 years) GBM patients with normofractionated or hypofractionated radiotherapy (RT) plus temozolomide (TMZ) based on Karnofsky performance status (KPS). Herein we report clinical outcomes in this cohort treated at our institute using this approach.Medical records of elderly GBM patients (≥60 years) treated between 2013 and 2017 with either normofractionated RT (59.4-60 Gy/30-33 fractions/6-6.5 weeks) or hypofractionated RT (35 Gy/10 fractions/2 weeks) plus TMZ were reviewed retrospectively. Outcomes of interest included progression-free survival (PFS), overall survival (OS), and ≥grade 3 myelotoxicity. Time-to-event outcomes were analyzed with Kaplan-Meier methods, compared using log-rank test, and reported as point estimates with 95% confidence interval (CI).The normofractionated cohort (n = 126) was characterized by a higher proportion of patients younger than age 65 years, KPS ≥70, methylated OOur single-institution clinical audit confirms poor survival in elderly GBM with suboptimal performance status but demonstrates acceptably fair outcomes in patients with preserved KPS comparable with the nonelderly cohort.

Background-Traditionally, endocrine therapy follows chemotherapy for hormone receptor (HR) positive breast cancer (BC) in the adjuvant setting. Concurrent chemo-hormonal therapy fell into disrepute due to previous studies showing a probable, small detriment in survival. (Albain et al, Lancet, 2009; Bedognetti et al, JNCI, 2009; Pico et al, Ann Oncol, 2004) However, the early studies are fraught with biases. The biological rationale was that endocrine therapy is cytostatic, pushing cancer cells into G0 phase which was feared to reduce the efficacy of chemotherapy which is known to act best on rapidly dividing cells. Thus, the two mechanisms of actions were thought to be antagonistic. However, this fear may be irrational and evidence at molecular level is contradictory. The current sequential strategy delays the start of an equally effective treatment modality in HR+ BC patients. Recent studies have shown that concurrent chemo-endocrine therapy is safe in metastatic HR+ setting. (Sledge et al, J Clin Oncol, 2000) One also needs to rethink neoadjuvant strategies in these patients to improve the current dismal pathological complete response (pCR) rates in this subset. (Cortazar et al, Lancet, 2014) Concurrent treatment seems to have improved pCR rate. (Sagiu K et al, Acta Med Okayama, 2015) Here, we describe a phase III, randomized study aimed to evaluate the efficacy of concurrent chemo-endocrine therapy in the adjuvant and neoadjuvant setting. (CTRI/2018/09/015643) Aims and Objectives- The primary objective is to assess the improvement in disease-free survival by administering concurrent versus sequential, (neo) adjuvant chemo-endocrine therapy in HR+, HER2 negative, non-metastatic BC. The secondary objectives are to assess improvement in overall survival, pCR rates, breast conservation rates. Biomarkers of response to treatment and tumour dormancy in HR+ BC will be studied in a subset of patients.Patients and methods-This is a prospective, open label study where non-metastatic, biopsy proven, HR+, HER2- BC patients who warrant chemotherapy in the adjuvant or neoadjuvant setting are considered. The study started accrual in December 2018 and 285 patients are randomized till date. Pregnant or lactating women and those with inflammatory breast carcinoma are excluded. After obtaining informed consent, patients are randomized to receive concurrent versus sequential chemo-endocrine treatment. Patients will receive all chemo and endocrine therapy as per the institutional standard protocols otherwise. Stratification criteria are neoadjuvant vs adjuvant therapy, pre vs postmenopausal status, node positive vs node negative status, 1st gen (anthracyclines alone) versus 2nd gen (including taxanes) chemotherapy. A two-sided log-rank test with an overall sample size of 2316 (2432 with a 5% dropout rate) (1158 in control and 1158 in treatment group) achieves 80% power at a 0.05 significance level to detect a hazard ratio of 0.80 when the proportion surviving in the control group is 0.70. An interim with respect to safety is planned in the protocol. Expected results and conclusion-Ours is a large, prospective trial evaluating the efficacy of concurrent chemo-endocrine therapy in HR+ BC patients. This has the potential to improve pCR rates in the neoadjuvant setting and change the standard of care in the management of HR+ BC patients. The biomarker analysis will help us further understand the biology of HR+ BC and shed light upon tumour dormancy signatures. Citation Format: Shalaka Joshi, Sridevi Murali-Nanavati, Vaibhav Vanmali, Rohini Hawaldar, Mujahid Gafur Shaikh, Mohammad Sadique Ansari, Sushmita Rath, Jaya Ghosh, Seema Gulia, Jyoti Bajpayi, Nita Nair, Vani Parmar, Purvi Thakkar, Garvit Chitkara, Tanuja Shet, Sangeeta Desai, Ayushi Sahay, Sudeep Gupta, Rajendra Badwe. Concurrent versus sequential chemo-endocrine therapy in er positive and her2 negative non-metastatic breast cancer- an open-label, phase III, randomized controlled trial [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-08-01.

Immunohistochemistry (IHC) is an essential tool available to pathologists for facilitating diagnosis and as well as guiding the prognosis of breast lesions. Newer markers are increasingly being added to the pathologists' armamentarium. However, the selection and interpretation of the IHC markers should be judicious. In light of an appropriate morphological assessment, they should complement each other and produce accurate reports. We have briefly outlined here the immunohistochemical approach used in the diagnosis and management of breast cancers at our tertiary care cancer center.

Purpose: Medulloblastomas, comprising 20%–25% of all primary brain tumors in children are much rarer in adulthood. Disease biology varies substantially across different age groups; however, owing to rarity, adults with medulloblastoma are traditionally treated using pediatric protocols. This is a retrospective audit of adolescent and adult medulloblastoma from a comprehensive cancer center. Methods: Data regarding demography, clinical presentation, imaging characteristics, histopathological features, molecular profiling, risk stratification, treatment details, and outcomes were retrieved from medical records. All time-to-event outcomes were analyzed using Kaplan–Meier method and compared with the log-rank test. Univariate and multivariate analysis of relevant prognostic factors was done with p value

Purpose and background: Isocitrate dehydrogenase (IDH) mutation and O-6 methyl guanine methyl transferase (MGMT) methylation are surrogate biomarkers of improved survival in gliomas. This study aims at studying the ability of semantic magnetic resonance imaging (MRI) features to predict the IDH mutation status confirmed by the gold standard molecular tests. Methods: The MRI of 148 patients were reviewed for various imaging parameters based on the Visually AcceSAble Rembrandt Images (VASARI) study. Their IDH status was determined using immunohistochemistry (IHC). Fisher’s exact or chi-square tests for univariate and logistic regression for multivariate analysis were used. Results: Parameters such as mild and patchy enhancement, minimal edema, necrosis < 25%, presence of cysts, and less rCBV (relative cerebral blood volume) correlated with IDH mutation. The median age of IDH-mutant and IDH-wild patients were 34 years (IQR: 29–43) and 52 years (IQR: 45–59), respectively. Mild to moderate enhancement was observed in 15/19 IDH-mutant patients (79%), while 99/129 IDH-wildtype (77%) had severe enhancement (p-value

Sporadic cerebellar hemangioblastomas are rare with majority of these tumors presenting as a part of von Hippel-Lindau syndrome. We demonstrate an unusual case of a symptomatic sporadic cerebellar hemangioblastoma mimicking a meningioma on MRI and 68 Ga-DOTANOC PET imaging.

Endolymphatic sac tumour (ELST) is a rare low-grade locally aggressive neoplasm arising from the endolymphatic duct or sac. It presents mostly with vestibulo-cochlear symptoms either sporadically or as part of von Hippel–Lindau (VHL) syndrome. Micro-neurosurgical excision remains the cornerstone of therapy with the role of radiotherapy (RT) being controversial. This is a clinico-pathological analysis of consecutive ELST patients presenting to a single-institution in India. Neuropathology database of a tertiary-care comprehensive cancer centre was searched electronically to identify consecutive patients with histopathological diagnosis of ELST registered at the institute over last one decade. Data regarding demographic profile, clinical presentation, histopathological features, treatment details and outcomes were retrieved from electronic medical records for this retrospective analysis. Electronic search identified seven unique patients with biopsy-proven ELST registered at the institute between 2009 and 2020. Median age of the study cohort was 39 years (range 24–65 years) with strong male predilection (5:2 ratio) and left-sided preponderance (71%). Most common presenting symptoms were hearing loss (86%) and earache (71%) on affected side followed by headache (43%). All patients underwent maximal safe resection at initial diagnosis and were followed-up closely with periodic surveillance imaging. Two patients underwent salvage RT using high-precision conformal techniques at recurrence/progression. ELST is a rare low-grade locally aggressive neoplasm that arises generally as part of VHL syndrome or sometimes sporadically. Gross total resection provides the best chance of cure with RT being reserved for unresectable disease, large residue, medical inoperability, or as salvage therapy for recurrent/progressive tumor.

To evaluate quality of life (QOL) and activities of daily living (ADL) longitudinally in patients treated with salvage re-irradiation for recurrent/progressive glioma. Secondary end points included post-re-irradiation survival.Patients with diffuse glioma, aged 18-70 years with preserved performance status and unequivocal evidence of recurrence/progression with a minimum 2-year time interval from index radiation therapy were eligible. QOL was assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core-30 (QLQ-C30) and brain cancer module (BN20). ADL was assessed using a modified Barthel's index. Assessments were carried out longitudinally, first before re-irradiation, at completion of re-irradiation and subsequently periodically on follow-up. Summary scores were calculated from raw scores as per the EORTC scoring manual; higher functional scores and lower symptom scores indicating better QOL. Summary mean scores for the modified Barthel's index were also calculated, with lower scores indicating higher disability. Differences between the summary scores at different time points were tested using the Friedman test.In total, 225 assessments were carried out in 60 patients accrued on the study. A significant improvement in scores was noted for physical function (P 0.001), emotional function (P = 0.002), cognitive function (P = 0.009) and social functioning (P = 0.047) over time. Role function scores (P = 0.182) and global health status scores (P = 0.074) remained stable. Among symptom scores, fatigue showed a statistically significant improvement over time (P = 0.01), whereas other symptom scores remained largely stable. There was a significant increase in the modified Barthel's index score over time (P = 0.001), suggesting greater functional independence. At a median follow-up of 12.9 months, the 1-year Kaplan-Meier estimates with 95% confidence intervals of post-re-irradiation progression-free survival and overall survival were 45.1% (31.5-58.7%) and 62.2% (49.2-75.2%), respectively.High-dose salvage re-irradiation in carefully selected patients with recurrent/progressive glioma is associated with stable QOL (preserved functional domains and reduced symptom burden) and improvement in ADL (greater functional independence) over time with encouraging survival outcomes.

Grading of gliomas is a piece of critical information related to prognosis and survival. Classifying glioma grade by semantic radiological features is subjective, requires multiple MRI sequences, is quite complex and clinically demanding, and can very often result in erroneous radiological diagnosis. We used a radiomics approach with machine learning classifiers to determine the grade of gliomas. Eighty-three patients with histopathologically proven gliomas underwent MRI of the brain. Whenever available, immunohistochemistry was additionally used to augment the histopathological diagnosis. Segmentation was performed manually on the T2W MR sequence using the TexRad texture analysis softwareTM, Version 3.10. Forty-two radiomics features, which included first-order features and shape features, were derived and compared between high-grade and low-grade gliomas. Features were selected by recursive feature elimination using a random forest algorithm method. The classification performance of the models was measured using accuracy, precision, recall, f1 score, and area under the curve (AUC) of the receiver operating characteristic curve. A 10-fold cross-validation was adopted to separate the training and the test data. The selected features were used to build five classifier models: support vector machine, random forest, gradient boost, naive Bayes, and AdaBoost classifiers. The random forest model performed the best, achieving an AUC of 0.81, an accuracy of 0.83, f1 score of 0.88, a recall of 0.93, and a precision of 0.85 for the test cohort. The results suggest that machine-learning-based radiomics features extracted from multiparametric MRI images can provide a non-invasive method for predicting glioma grades preoperatively. In the present study, we extracted the radiomics features from a single cross-sectional image of the T2W MRI sequence and utilized these features to build a fairly robust model to classify low-grade gliomas from high-grade gliomas (grade 4 gliomas).

To report survival outcomes and identify prognostic factors of salvage re-irradiation (re-RT) in recurrent/progressive glioma. Medical records of patients treated with high-dose re-RT as part of multi-modality salvage therapy for recurrence/progression of adult diffuse glioma from 2010 to 2019 were analyzed retrospectively. A total of 111 patients developing recurrent/progressive high-grade glioma after adequate upfront treatment at initial diagnosis were included. The first course of radiotherapy (RT) had been delivered to a median dose of 59.4 Gy with an inter-quartile range (IQR) of 54-60 Gy. Median time to recurrence/progression was 4.3 years (IQR = 2.3–7.4 years) while the median time to re-RT was 4.8 years (IQR = 3.6–7.9 years). Re-RT was delivered with intensity-modulated radiation therapy (IMRT) using 1.8 Gy/fraction to a median dose of 54 Gy (IQR = 50.4–55.8 Gy) for a cumulative median equivalent dose in 2-Gy fractions (EQD2) of 104.3 Gy (IQR = 102.6–109.4 Gy). At a median follow-up of 14 months after re-RT, the 1-year Kaplan–Meier estimates of post-re-RT progression-free survival (PFS) and overall survival (OS) were 42.8 and 61.8%, respectively. Univariate analysis identified histological grade at recurrence/progression; histological subtype; disease-free interval (DFI) and time interval between both courses of RT; performance status at re-RT; dose at re-RT and cumulative EQD2; isocitrate dehydrogenase (IDH) mutation; and O6-methyl-guanine DNA methyl transferase (MGMT) gene promoter methylation as significant prognostic factors. Preserved performance status, longer DFI, prolonged time interval between both courses of RT, and presence of IDH mutation were associated with significantly improved PFS on multi-variate analysis. However, only performance status retained independent prognostic significance for OS on multi-variate analysis. Post-treatment changes were seen in 33 (30%) patients on follow-up imaging, with higher cumulative dose (EQD2 ≥ 104.3 Gy) being associated with increased risk of post-re-RT pseudo-progression. This clinical audit reports encouraging survival outcomes and identifies key prognostic factors associated with high-dose salvage re-RT in recurrent/progressive glioma.

Central neurocytoma is a rare benign brain tumor that typically arises from the subependymal lining of the lateral ventricles in young adults and is generally associated with excellent survival following neurosurgical excision alone. This is a retrospective clinical audit of biopsy-proven neurocytoma registered between 2004 and 2019 at a single institution in India. All time-to event outcomes were analyzed using Kaplan-Meier method and compared with the log-rank test. Any p-value0.05 was considered statistically significant. A total of 66 patients with neurocytoma were included in the descriptive analysis. Median age of study cohort was 31 years with equitable gender ratio. Majority (83%) of tumors were intraventricular, lateral ventricle being the commonest location. Following maximal safe resection, patients were generally kept on close clinico-radiological surveillance. Most patients (80%) had typical World Health Organization (WHO) grade II neurocytoma with remaining 20% showing histological atypia and/or high-grade features. Outcome analysis was restricted to 35 patients with relevant treatment details and adequate follow-up information. Six patients experienced recurrent/progressive disease with 2 documented deaths. At a median follow up of 52 months, 5-year Kaplan-Meier estimates of progression-free survival and overall survival were 93.3% and 96.8% respectively. Three patients developed delayed recurrence (5-years after initial diagnosis) underscoring the importance of long-term follow-up. Atypical/high-grade histology was associated with inferior survival that may stand to benefit with upfront adjuvant radiotherapy. This represents the largest single-institution series of central neurocytoma and demonstrates excellent outcomes with adequate surgical resection alone, reserving radiotherapy for large residual tumor, recurrent disease, and/or atypical high-grade histology.

BACKGROUND AND PURPOSE Differentiating tumor recurrence (TR) from radiation necrosis (RN) in high grade glioma (HGG) following radiotherapy can be challenging. The ability of conventional magnetic resonance imaging (MRI) to differentiate TR from post-therapeutic effects is often limited. Multiparametric advanced MRI (perfusion) and positron emission tomography (PET) with amino acid tracers, specifically 18F-Fluoroethyl-Tyrosine (FET) can provide relevant additional information on tumor metabolism, which allows for a more accurate diagnosis to differentiate tumor recurrence from radiation necrosis in high grade gliomas. MATERIALS AND METHODS Prospective analysis of 62 lesions in 62 patients with HGG who underwent both MRI and FET-PET imaging within three weeks intervals was done independently by a neuroradiologist and nuclear medicine physician. The study was conducted in a tertiary care oncology center between July 2018 and August 2021. Manually segmented regions of interest were placed over the areas of maximum enhancement/suspicion on MRI and FET uptake, which were used to calculate the relative cerebral volume (rCBV) and tumor to background ratios, respectively. Definitive diagnosis (TR versus RN) was made on clinico-radiological follow-up or histopathological report (wherever available). RESULTS Out of the 62 lesions that were studied, 46 and 16 had TR and RN, respectively. The sensitivity and specificity for determination of TR in HGG with conventional MRI were 98% and 62.5% respectively, while with FET-PET it was 91% and 87.5% respectively. The PPV , NPV and accuracy for MRI were 88%, 91% , 89% , while for FET-PET it was 95%, 78% and 90% respectively. A combination of MRI and PET parameters (mean target-to-background ratio), demonstrated an increase in diagnostic accuracy to 97%. CONCLUSION Cumulative imaging with MRI and FET-PET offers a multiparametric assessment of glioma recurrence that is correlative and complimentary, with higher accuracy and clinical value.

Objective: Image-based prediction of molecular subgroups of Medulloblastoma (MB) has the potential to optimize and personalize therapy. The objective of the study is to distinguish between broad molecular subgroups of MB using MR–Texture analysis. Methods: Thirty-eight MB patients treated between 2007 and 2020 were retrospectively analyzed. Texture analysis was performed on contrast enhanced T1(T1C) and T2 weighted (T2W) MR images. Manual segmentation was performed on all slices and radiomic features were extracted which included first order, second order (GLCM - Grey level co-occurrence matrix) and shape features. Feature enrichment was done using LASSO (Least Absolute Shrinkage and Selection Operator) regression and thereafter Support Vector Machine (SVM) and a 10-fold cross-validation strategy was used for model development. The area under Receiver Operator Characteristic (ROC) curve was used to evaluate the model. Results: A total of 174 and 170 images were obtained for analysis from the Axial T1C and T2W image datasets. One hundred and sixty-four MR based texture features were extracted. The best model was arrived at by using a combination of 30 GLCM and six shape features on T1C MR sequence. A 10-fold cross-validation demonstrated an AUC of 0.93, 0.9, 0.93, and 0.93 in predicting WNT, SHH, Group 3, and Group 4 MB subgroups, respectively. Conclusion: Radiomic analysis of MR images in MB can predict molecular subgroups with acceptable degree of accuracy. The strategy needs further validation in an external dataset for its potential use in ab initio management paradigms of MBs. Advances in knowledge: Medulloblastoma can be classified into four distinct molecular subgroups using radiomic feature classifier from non-invasive Multiparametric Magnetic resonance imaging. This can have future ramifications in the extent of surgical resection of Medulloblastoma which can ultimately result in reduction of morbidity.

Carcinoma of breast with neuroendocrine differentiation is an extremely rare entity, especially in male population. Although the "garden variety" of male breast cancers is often metastatic at presentation, with an aggressive course, there is hardly any literature about neuroendocrine variants. We report a case of a 57-year-old man who had pituitary symptoms, which on 68Ga-DOTANOC PET/CT imaging turned out to be a metastatic lesion, with somatostatin expressing primary in breast and other sites, with histopathological confirmation of neuroendocrine differentiation in breast cancer.

Objectives. Atypical teratoid/rhabdoid tumor (AT/RT) is a rare malignant pediatric brain tumor, characterized by inactivation of INI1/hSNF5 gene and loss of its protein. We studied the histomorphological and immunohistochemical spectrum of this tumor including cyclin D1 expression and MYC gene amplification. Methods. Cases with INI1 loss by immunohistochemistry (IHC; from 2005 to 2018) were retrieved, reviewed, and evaluated for cyclin D1 expression by additional IHC and fluorescence in situ hybridization for MYC genes. Results. A total of 66 cases were identified. Age ranged from 1 to 20 years (≤3 years, 44 cases; >3 years, 22). Male to female ratio was 1.7:1. Tumor locations were as follows: posterior fossa: 30; supratentorial: 31; spinal: 5. AT/RT in patient ≤3 years was frequently located in the posterior fossa, composed of primitive embryonal morphology ( P = .02), rarely had ample rhabdoid cells ( P = .05), and had a negative impact on overall survival ( P = .04). The rhabdoid cells was a conspicuous component of posterior fossa tumors compared with the supratentorial ones ( P = .06). The supratentorial tumors ( P = .06), absence of rhabdoid cells ( P = .06), and the presence of immunological divergent differentiation ( P = .11) had a comparatively better outcome. Cyclin D1 overexpression (n = 46) was noted in 32 cases and was frequently seen in the posterior fossa tumors ( P = .02). CMYC (n = 42) amplification was seen in 1 case and the NMYC (n = 42) amplification in none. Conclusion. AT/RT can occur in the noninfantile age group, at nonconventional sites and frequently overexpress cyclin D1. The MYC alterations are almost nonexistent in AT/RT.

BACKGROUND: Medulloblastoma (MB) is a heterogeneous disease comprising 4 molecular subgroups - wingless (WNT), sonic hedgehog, Group 3, and Group 4 tumors - with distinct developmental origins, diverse clinico-demographic characteristics, unique transcriptional profiles, and widely varying outcomes. WNT-MB is associated with the best outcomes (5-year survival >90%) prompting attempts at treatment de-escalation to reduce late toxicity. We undertook a clinical audit of WNT-MB patients treated at our tertiary-care comprehensive cancer centre. METHODS: Patients with molecularly confirmed WNT-MB treated with maximal safe resection followed by post-operative standard-of-care risk-stratified adjuvant radio(chemo)therapy were identified retrospectively via electronic search of the neuro-oncology database. Data regarding clinico-demographic characteristics, histo-molecular features, treatment details, patterns of failure, and survival outcomes was retrieved from electronic medical records and/or hospital case files. Time-to-event outcomes were analyzed using Kaplan-Meier methods and compared with the log-rank test. RESULTS: Between 2004 to 2018, a total of 65 patients of WNT-MB were registered at our institute. Five patients treated on a prospective clinical trial of therapy de-intensification were excluded leaving 60 patients that constitute the present study cohort. Median age at presentation was 12 years (inter-quartile range 9-18 years) with male preponderance (2:1). Six patients (1 post-operative mortality and 5 without adequate details of treatment or outcomes) were excluded from the survival analysis which was restricted to 54 patients. At a median follow-up of 66 months, Kaplan-Meier estimates of 5-year progression-free survival and overall survival were 87.9% and 92.8% respectively. Traditional high-risk features such as age, residual tumor (>1.5cm2) and leptomeningeal metastases (M+) did not emerge as significant prognostic factors for survival in this molecularly-characterized WNT-MB cohort. CONCLUSION: WNT-MB patients have excellent survival outcomes irrespective of traditional high-risk features suggesting the need for more tailored and refined risk-stratification with potential de-intensification of therapy. ACKNOWLEDGEMENTS: Brain Tumor Foundation (BTF) of India

INTRODUCTION The NCCN recommends either PCV (Procarbazine, CCNU and vincristine) or Temozolomide (TMZ) as adjuvant therapy in high-risk grade 2 & grade 3 gliomas. In this ongoing study we are comparing PCV with TMZ as adjuvant therapy in this setting. METHODS This is a randomised phase 3 study that includes patients with high risk (as per RTOG) grade 2 gliomas and grade 3 gliomas after surgery. Patient are randomly assigned in 1: 2 to receive either adjuvant PCV or TMZ after adjuvant RT. The primary end-point is progression-free survival & key secondary end points are overall survival, toxicity and quality of life. The current analysis focuses on the compliance and adverse events seen in patients enrolled till 30th April 2020. RESULTS 46 patients were enrolled, with 30 patients in TMZ arm. The median age of patients was 37 years (range 23-64). The ECOG PS was 1 in 45 (97.8%) patients and 2 in 1(2.2%) patient at enrolment. The number of patients who have completed all planned cycles of chemotherapy in the PCV arm is 62.5% (10, n=16) as compared to 90% (27, n=30) in the TMZ arm (P=0.047). The incidence of grade 3 or higher adverse events is 68.8% (n=11) in the PCV arm and 16.7% (n=5) in the TMZ arm (P=0.001). The most common grade 3 or higher toxicities noted are lymphopenia in 50% (n=8), neutropenia in 37.5% (n=6), and thrombocytopenia in 25% (n=4) in the PCV arm; while the corresponding numbers in the TMZ arm are 13.3% (n=4), 3.3% (n=1) and 10% (n=3) respectively. CONCLUSION In the current study the chemotherapy completion rates are higher with TMZ and it is associated with lower grade 3-4 events, whether this will lead to an improvement in outcomes remains to be seen.

INTRODUCTION Little is known about tumour-infiltrating lymphocytes (TILs) in brain metastasis (BM) and their utility as predictive biomarker for immunotherapy. AIM: To analyze TILs in BM, and correlate with corresponding paired primary (PP). METHODS Inclusion: Histologically confirmed BM and PP (2015-2020). Exclusion: Hematological malignancies, spinal cord/meningeal metastasis, pediatric age, slides/blocks not available. Final Nf 277 BM; 64 PP. One H&E slide from both PP &BM assessed for stromal TILs (sTILs) and intratumoral TILs (iTILs) as per International TIL Working Group guidelines. RESULTS Median sTILs (10%) were significantly higher than iTILs (1%) in primary and BM (p-value < 0.001). sTILs were mild ( lower to higher (33.33%). Conversion rate higher for breast (54.3%) &GIT (62.5%) than lung (45.5%) &GUT (40%). In BM, preoperative steroid therapy (PST) showed lower sTILs (≤10%) (p-value= 0.041), and adenocarcinoma histology higher sTILs ( >10%) (p-value= 0.001), while precocious metastasis (p-value= 0.051) and absence of extracranial metastasis (p-value= 0.083) trended towards higher sTILs. Median survival of whole cohort was 20 months (95% CI 14.4-25.68 months). Presence of extracranial metastasis (p-value= 0.01); precocious BM (p-value= 0.007) showed lower overall survival (OS), while adenocarcinoma histology better OS (p-value= 0.029), in both univariate and multivariate analysis. Absence of PST showed longer median survival, though not significant (24.1 vs 19.8months; p-value= 0.19). CONCLUSIONS sTILs predominantly show high >low conversion between PP and BM, signifying lowered immune response in BM. Thus, evaluation of sTILs in BM, wherever tissue available, may be indicated if immunotherapy is considered. Parameters with higher sTILs showed longer survival, possibly indicating prognostic role of tumor microenvironment in BM.

Purpose/Objective(s) Re-irradiation (ReRT) is often used to treat recurrent high grade glioma (HGG). There is limited literature regarding the patterns of recurrence following ReRT, which was investigated in the current study. Materials/METHODS Patients with available radiation (RT) contours, dosimetry, and imaging-based evidence of recurrence were included in the retrospective study. All patients were treated with fractionated RT using conformal technique. Recurrence was documented as per decision in tumor board based on imaging with magnetic resonance imaging (MRI) or Flouroethyl-L-Tyrosine (FET) positron emission tomography (PET), which was registered with the planning CT. Failure patterns were classified as in-field, marginal, and out-field as decided by >50% recurrence volume within 95%, 20-95%, and outside 20% isodose lines, respectively. RESULTS Study population included 37 patients treated with median dose of 54 Gy (range 50.4-54 Gy). Before ReRT, 92% patients had undergone surgery (biopsy in 3, gross total resection in 9, subtotal resection in 22), 62% received concurrent chemo with ReRT, and 49% received maintenance chemotherapy. Median time to recurrence was 9 months (7-16 months, median 10 and 8 months respectively for in-field and marginal/out-field recurrence). In-field, marginal, and out-field recurrence were seen in 24 (65%), 10 (27%), and 3 (8%), respectively. Recurrence mapping was done using MRI, PET, or both in 27, 3, and 7, respectively. Of 24 patients with in-field recurrence, 8 and 16 had disease volume within gross tumor volume and clinical target volume, respectively. 2 patients had leptomeningeal dissemination (1 with majority of recurrence volume in-field and 1 with marginal failure in addition to metastatic disease). CONCLUSION Following ReRT for HGG, the majority of recurrence was in the high dose region, suggesting the use of conservative target volumes. Future studies are required for feasibility of dose-escalation to improve control rates, particularly in patients with long intervals from first course of RT.

INTRODUCTION In patients treated with radiation (RT), doses to hippocampus influence neurocognitive outcomes. However, the role of hippocampal subvolumes in memory functioning has not been reported, which prompted the current study. METHODS Adults ( > 18 years) with pituitary tumors treated with fractionated RT (45 Gy/ 25 fractions/ 5 weeks) were accrued in the prospective study. Hippocampus was delineated on T1-weighted 3D-FSPGR sequences with 1mm slice thickness. The head, body, and tail of hippocampus were drawn for the current study based on the consensus of two neuroradiologists. The anatomical landmarks were: head (basilar artery to interpeduncular cistern), body (interpeduncular cistern to superior colliculus), and tail (beyond superior colliculus). Memory assessment was done pre-RT and 18 months post-RT by dedicated neuropsychologist using Weschler Memory Scale. The dose-volume parameters (maximum, mean, D10-D100) were extracted from bilateral hippocampus and subvolumes individually, which were correlated with the memory outcomes. Binary endpoints of > 5% drop of memory quotient (MQ) or not at 18 months were used for analysis using an independent t-test or Mann Whitney test as appropriate. RESULTS Of 25 patients included in the analysis, 11 had drop of MQ > 5% at 18 months. The left and right hippocampus doses of D10, D20, and D30 were significantly higher in patients with higher memory decline. For the subvolumes, only dose to bilateral head had statistically significant impact on MQ. Mean doses for patients with > 5% MQ drop for left and right heads were 26 Gy and 24 Gy compared to 21 Gy and 19 Gy, respectively, for the other group. CONCLUSION Doses to bilateral hippocampus were shown to impact short-term memory. Of the subvolumes, only head appeared significant in memory functioning from the current pilot study, opening a window for exploring stricter dose constraints towards hippocampal head for primary or metastatic brain tumors.

Background Imaging features are known to reflect inherent disease biology in various cancers including brain tumors. We report prognostic impact of magnetic resonance imaging (MRI) features on survival in patients with medulloblastoma treated between 2007 and 2018 at our institute. Methods Sixteen semantic imaging features (with pre-defined categories) were extracted from pre- and post-contrast T1-weighted and T2-weighted MRI by consensus. Univariate analysis and multivariate Cox regression analysis were performed to assess correlation of semantic features with relapse-free survival (RFS) and overall survival (OS). Results The study cohort comprised of 171 medulloblastoma patients (median age 9 years) treated with maximal safe resection followed by risk-stratified adjuvant radio(chemo)therapy. A total of 55 patients experienced recurrent/progressive disease (commonly neuraxial metastases) resulting in 44 deaths including one treatment-related death. At a median follow-up of 45 months (inter-quartile range 19–65 months), 5-year Kaplan-Meier estimates of RFS and OS were 64% and 71%, respectively. Semantic MRI features such as non-central tumor location on vertical axis, absence of brainstem involvement, ≤ 80% solid tumor area with contrast-uptake, heterogenous pattern of contrast-enhancement, necrosis, calcification, and T2-weighted heterogeneity were associated with significantly worse RFS and/or OS on univariate analysis. Cox regression analysis identified tumor location on the vertical axis, brainstem involvement, and calcification as independent prognostic factors impacting outcomes. Distinctive MRI features correlated with survival even within individual molecular subgroups of medulloblastoma. Conclusion Distinctive semantic MRI features correlate significantly with survival outcomes in medulloblastoma including within individual molecular subgroups reflecting their prognostic impact that transcends radiogenomic correlation.

Background and purpose Highergrade glial neoplasms undergo standard treatment with surgery, radiotherapy, and alkylating agents. There is often a clinical/neuroimaging dilemma in the post-treatment setting to differentiate disease recurrence from treatment-related changes. FET (fluoro-ethyl-tyrosine) PET has emerged as a molecular imaging modality for cases where MR imaging is inconclusive. This study aims to develop a cutoff on FET PET for differentiating true recurrence from post-treatment changes. Methods We retrospectively analyzed72 patientswith post-treatment grade 3 or 4 brain gliomas. Five to six mCi of 18 F-FET was injected and static imaging of the brain was performed at 20 min. A tumor-to-white matter (T/Wm) ratio was used as semiquantitative parameter. A T/Wm cutoff of 2.5 was used for image interpretation. Imaging findings were confirmed by either histopathologic diagnosis in a multidisciplinary joint clinic or based on follow-up of clinical and neuroimaging findings. Results Forty-one of 72 patients (57%) showed recurrent disease on FET PET. Thirty-five of them were confirmed to have tumor recurrence; six patients showed post-treatment changes. Thirty-one of 72 patients (43%) showed post-treatment changes on FET PET; 27 were confirmed as post-treatment change and four patients had tumor recurrence on subsequent MR imaging. An optimum T/Wm cutoff of 2.65 was derived based on receiver operating characteristic analysis with a sensitivity of 80% and specificity of 87.5%. Conclusion Static FET PET can be used as problem-solving imaging modality with a T/Wm cutoff of 2.65 to differentiate late recurrence from post-treatment changes in grade 3 or 4 brain gliomas with equivocal MR features.