Clinico-Radiological Outcomes in WNT-Subgroup Medulloblastoma.

Medulloblastoma (MB) comprises four broad molecular subgroups, namely wingless (WNT), sonic hedgehog (SHH), Group 3, and Group 4, respectively, with subgroup-specific developmental origins, unique genetic profiles, distinct clinico-demographic characteristics, and diverse clinical outcomes. This is a retrospective audit of clinical outcomes in molecularly confirmed WNT-MB patients treated with maximal safe resection followed by postoperative standard-of-care risk-stratified adjuvant radio(chemo)therapy at a tertiary-care comprehensive cancer centre. Of the 74 WNT-MB patients registered in a neuro-oncology unit between 2004 to 2020, 7 patients accrued on a prospective clinical trial of treatment deintensification were excluded, leaving 67 patients that constitute the present study cohort. The median age at presentation was 12 years, with a male preponderance (2:1). The survival analysis was restricted to 61 patients and excluded 6 patients (1 postoperative mortality plus 5 without adequate details of treatment or outcomes). At a median follow-up of 72 months, Kaplan-Meier estimates of 5-year progression-free survival and overall survival were 87.7% and 91.2%, respectively. Traditional high-risk features, large residual tumour (≥1.5 cm2), and leptomeningeal metastases (M+) did not significantly impact upon survival in this molecularly characterized WNT-MB cohort treated with risk-stratified contemporary multimodality therapy. The lack of a prognostic impact of conventional high-risk features suggests the need for refined risk stratification and potential deintensification of therapy.

Post-ictal changes presenting as late pseudoprogression on MRI and PET in a patient with diffuse glioma: Case report and brief literature review.

Following completion of adjuvant radiation and chemotherapy imaging surveillance forms a major role in the management of diffuse gliomas. The primary role of imaging is to detect recurrences earlier than clinical symptomatology. Magnetic resonance imaging (MRI) is considered the gold standard in follow-up protocols owing to better soft tissue delineation and multiparametric nature. True recurrence can often mimic treatment-related changes, it is of paramount importance to differentiate between the two entities as the clinical course is divergent. Addition of functional sequences like perfusion, spectroscopy and metabolic imaging can provide further details into the microenvironment. In equivocal cases, a follow-up short interval imaging might be obtained to settle the diagnostic dilemma. Here, we present a patient with diagnosis of recurrent oligodendroglioma treated with adjuvant chemoradiation, presenting with seizures five years post-completion of chemotherapy for recurrence. On MRI, subtle new onset gyral thickening of the left frontal region with mild increase in perfusion and patchy areas of raised choline. FET-PET (fluoro-ethyltyrosine) showed an increased tumour-to-white matter (T/Wm) ratio favouring tumour recurrence. Based on discussion in a multi-disciplinary joint clinic, short interval follow-up MRI was undertaken at two months showing decrease in gyral thickening and resolution of enhancing areas in left frontal lobe. Repeat imaging one year later demonstrated stable disease status without further new imaging findings. Given the changes resolving completely without any anti-tumoral intervention, we conclude this to be peri-ictal pseudoprogression, being the second such case described in India.

Diagnostic Performance of Response Assessment FDG-PET/CECT in HNSCC Treated With Definitive Radio(chemo)therapy Using NI-RADS.

OBJECTIVE: To assess the diagnostic performance of response assessment 18F-fluorodeoxyglucose positron emission tomography/contrast-enhanced computed tomography (FDG-PET/CECT) following definitive radio(chemo)therapy in head and neck squamous cell carcinoma (HNSCC) using Neck Imaging Reporting and Data System (NI-RADS). STUDY DESIGN: A retrospective analysis from a prospectively maintained dataset. SETTING: Tertiary-care comprehensive cancer center in a low-middle-income country. METHODS: Adults with newly diagnosed, biopsy-proven, nonmetastatic HNSCC treated with definitive radio(chemo)therapy were included. Posttreatment response assessment FDG-PET/CECT scans were retrospectively assigned NI-RADS categories (1-3) for the primary site, neck, and both sites combined. Locoregional recurrence occurring within 2-years was defined as the event of interest. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy were calculated. Locoregional control stratified by NI-RADS categories was computed with the Kaplan-Meier method and compared using the log-rank test. RESULTS: Posttreatment FDG-PET/CECT scans were available in 190 patients constituting the present study cohort. Sensitivity, specificity, PPV, NPV, and overall accuracy of the NI-RADS template for the primary site was 73.5%, 81.4%, 46.3%, 93.4%, and 80.0%, respectively. Similar metrics for the neck were 72.7%, 87.5%, 43.2%, 96.1%, and 85.8%, respectively. Combining primary site and neck, the corresponding metrics of diagnostic accuracy were 84.4%, 69.7%, 46.3%, 93.5%, and 73.2%, respectively. At a median follow-up of 40 months, Kaplan-Meier estimates of 2-year locoregional control were significantly higher for NI-RADS category 1 (94.2%) compared to NI-RADS category 2 (69.4%) and category 3 (20.4%), respectively (stratified log-rank p < .0001). CONCLUSION: FDG-PET/CECT using the NI-RADS template is associated with good diagnostic performance and prognostic utility in HNSCC treated with definitive radio(chemo)therapy.

Optimizing Postoperative Adjuvant Therapy in Elderly Patients with Newly Diagnosed Glioblastoma: Single-Institution Audit of Clinical Outcomes from a Tertiary-Care Comprehensive Cancer Center in India.

BACKGROUND: 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. METHODS: 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). RESULTS: The normofractionated cohort (n = 126) was characterized by a higher proportion of patients younger than age 65 years, KPS ≥70, methylated O6-methylguanine DNA methyltransferase (MGMT), and receiving adjuvant TMZ including extended adjuvant TMZ (>6 cycles) compared with the hypofractionated cohort (n = 20), confirming selection bias. At a median follow-up of 13 months, 1-year Kaplan-Meier estimates of PFS and OS were 43% (95% CI: 36%-52%) and 56% (95% CI: 48%-64%), yielding median PFS and OS of 11.0 months and 13.1 months, respectively. Higher KPS, methylated MGMT, normofractionated RT, and extended adjuvant TMZ emerged as favorable prognostic factors. TMZ was well tolerated with a low risk of ≥grade 3 myelotoxicity. CONCLUSIONS: Our 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.

Endolymphatic sac tumor: single-institution series of seven cases with updated review of literature.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Clinical Audit of Survival Outcomes and Prognostic Factors in Adolescents and Adults with Medulloblastoma.

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 <0.05 being considered statistically significant. Results: A total of 162 patients ≥15 years of age with medulloblastoma were included. The median age was 25 years (range: 15-59 years) with leptomeningeal metastases seen in 31 (19%) patients at initial diagnosis. Following surgery, patients were treated with appropriate risk-stratified adjuvant therapy comprising of craniospinal irradiation plus boost with or without systemic chemotherapy. At a median follow-up of 50 months, 5-year Kaplan-Meier estimates of progression-free survival and overall survival were 53.5% and 59.5%, respectively. The addition of adjuvant systemic chemotherapy did not impact upon survival in standard-risk medulloblastoma. High-risk (HR) disease and anaplastic histology emerged as significant and independent predictors of poor survival on multivariate analysis. Conclusion: Medulloblastoma is a rare tumor in adolescents and adults with key differences in disease biology and resultant outcomes compared with the pediatric population. Contemporary management comprising maximal safe resection followed by appropriate risk-stratified adjuvant therapy provides acceptable survival outcomes.

Distress Screening in Head and Neck Cancer Patients Planned for Cancer-Directed Radiotherapy.

OBJECTIVE/HYPOTHESIS: To estimate the prevalence of baseline clinically significant distress (distress score ≥ 4) in head and neck cancer patients planned and treated with radical intent radiotherapy using the National Comprehensive Cancer Network Distress Thermometer (DT) and assess factors predictive of distress. STUDY DESIGN: Cross-sectional study. METHODS: This was a cross-sectional study evaluating distress in 600 head and neck cancer patients undergoing radiation therapy. The DT was used to screen patients for distress at baseline before radiotherapy. RESULTS: The median distress score of the entire cohort was 4 interquartile range (IQR) (IQR: 3-5), and 340 patients (56.7%) had clinically significant distress. On univariate analysis, the causal factors predictive of distress were low socioeconomic status (P = .04), presence of proliferative growth at presentation (P = .008), site of the tumor (oral cavity, P = .02), comorbidity (P = .04), and presence of Ryle's tube or tracheostomy tube at baseline (P = .01). Low socioeconomic status was significant (P = .04) on multivariate analysis for high levels of distress. CONCLUSIONS: Among head and neck cancer patients, 56% of patients had clinically significant baseline distress, and patients with low socioeconomic status had high distress. There is a need for interventions to mitigate distress. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2023-2029, 2021.

Impact of comorbidity on therapeutic decision-making in head and neck cancer: audit from a comprehensive cancer center in India.

BACKGROUND: Head and neck cancer has increased incidence of comorbidity due to tobacco and alcohol use. METHODS: Two hundred consecutive patients were included in this cross-sectional study. Data on clinico-demographic characteristics and comorbidity was extracted from case records. Comorbidity was assessed with Adult Comorbidity Evaluation 27 (ACE-27) and Charlson Comorbidity Index (CCI). Change in therapeutic decision-making from institutional evidence-based guidelines was classified as low, medium, or high-impact. RESULTS: Of 200 patients, 68(34%) had comorbidity while 15 had multimorbidity. No change in therapeutic decision-making was seen in 139 patients (69.5%), 61patients (30.5%) had change from institutional evidence-based guidelines. There was strong positive correlation (Spearman's correlation coefficient = 0.80; p < .001) between ACE-27 and change in therapeutic decision-making. For CCI, there was moderate positive correlation (Spearman's correlation coefficient = 0.50; p < .001). CONCLUSION: Comorbidity in patients with head and neck cancer can influence therapeutic decision-making. Prospective longitudinal rigorous collection of comorbidity data is warranted for correlation with outcomes. ACE-27 may be a clinically more meaningful tool for comorbidity assessment.

Suprasellar ganglioglioma with unusual diffuse involvement of the entire optico-chiasmal hypothalamic pathway.

Gangliogliomas (GG) are mixed glioneuronal tumors of the central nervous system (CNS), occurring mostly in the pediatric population, with common sites being temporal lobes and less commonly in the frontal and parietal lobes. We report a case of a 7-year-old child who presented with bilateral visual defects for 6 months. Magnetic resonance imaging (MRI) of the brain revealed an intensely enhancing mass lesion with calcification in the sellar and suprasellar region involving the optic chiasm and the left optic nerve. The mass showed almost bilaterally symmetrical diffuse spread along the optic tracts posteriorly and hypothalamus, temporal lobes, thalami and the basal ganglia. The lesion was radiologically indistinguishable from chiasmatic astrocytoma or a germ cell tumor but histopathological features were of a ganglioglioma. While a few optic apparatus gangliogliomas have been reported in the literature, such widespread diffuse involvement of the entire optico-chiasmal hypothalamic pathway is unusual.