Understanding of molecular events underlying resistance and relapse in glioblastoma (GBM) is hampered due to lack of accessibility to resistant cells from patients undergone therapy. Therefore, we mimicked clinical scenario in an in vitro cellular model developed from five GBM grade IV primary patient samples and two cell lines. We show that upon exposure to lethal dose of radiation, a subpopulation of GBM cells, innately resistant to radiation, survive and transiently arrest in G2/M phase via inhibitory pCdk1(Y15). Although arrested, these cells show multinucleated and giant cell phenotype (MNGC). Significantly, we demonstrate that these MNGCs are not pre-existing giant cells from parent population but formed via radiation-induced homotypic cell fusions among resistant cells. Furthermore, cell fusions induce senescence, high expression of senescence-associated secretory proteins (SASPs) and activation of pro-survival signals (pAKT, BIRC3 and Bcl-xL) in MNGCs. Importantly, following transient non-proliferation, MNGCs escape senescence and despite having multiple spindle poles during mitosis, they overcome mitotic catastrophe to undergo normal cytokinesis forming mononucleated relapse population. This is the first report showing radiation-induced homotypic cell fusions as novel non-genetic mechanism in radiation-resistant cells to sustain survival. These data also underscore the importance of non-proliferative phase in resistant glioma cells. Accordingly, we show that pushing resistant cells into premature mitosis by Wee1 kinase inhibitor prevents pCdk1(Y15)-mediated cell cycle arrest and relapse. Taken together, our data provide novel molecular insights into a multistep process of radiation survival and relapse in GBM that can be exploited for therapeutic interventions.

Objective To assess the ability of 68Ga DOTA-NOC PET/computed tomography (CT) to differentiate dural metastases from meningioma. Patients and methods Patients who underwent a 68Ga DOTA-NOC PET/CT for differentiating meningiomas from dural metastases were included in the study. A visual score was assigned to the dural lesions (visual score – 1 to 3) in relation to the uptake in liver and spleen and variation in the visual score was evaluated. SUVmax of the dural lesions was also noted and difference in the values of the two pathologies were compared for statistical significance using nonparametric statistical tests. Final diagnosis was decided by histopathological confirmation whenever available. Results Imaging, histopathology or follow-up data of 42 patients was available for analysis. Meningioma was the final diagnosis in 31 (73.8%) patients, whereas dural metastases were diagnosed in 9 (21.4%) patients. In two patients, histopathology revealed inflammatory pseudotumor and hemangioblastoma. Meningiomas showed intense tracer uptake in 30/31 patients (visual score 3). All metastatic lesions showed some degree of tracer uptake though the intensity was lesser compared to meningioma (visual score 1, 2). Meningiomas showed a significantly higher median SUV max value compared to metastases (12.7 vs. 6.0, P = 0.001). Conclusion Meningiomas can be differentiated from dural metastases by virtue of their higher uptake of 68Ga-labeled DOTA peptides reflecting higher SSTR expression. An asymptomatic meningeal based lesion with a high visual score (Visual score 3) has a very high probability to be a meningioma rather than dural metastasis.

Central nervous system lymphomas can be differentiated from GBM and metastases by their higher metabolic activity. In addition, F-FDG PET/CT can potentially impact therapeutic decisions by detecting primary malignancy in patients with metastatic brain lesions and extracranial disease sites in patients with brain lymphoma.

BackgroundClassical Hodgkin lymphoma (cHL) has excellent survival rates, but late effects are an issue and dictate modern approaches. We analyzed the clinical profile and outcome of cHL treated on a risk‐adapted approach aimed at reducing late effects while improving historical outcomes at our center.ProcedureChildren (≤15 years) consecutively treated for cHL from January 2013 through December 2016 were retrospectively analyzed. 18FDG‐PET‐CT–based staging and response assessment was done after two cycles for early response (ERA) and end of chemotherapy (late‐response assessment [LRA]) if not in complete response (CR; Deauville < 4) at ERA. Stages IA/IB/IIA were low risk (LR) and received two cycles of ABVD (adriamycin/bleomycin/vinblastine/dacarbazine). Stages IAX/IBX/IIAX/IIB/IIIA were intermediate risk (IR), and stages IIBE/IIBX/IIIAE/IIIAX/IIIB/IVA/IVB were high risk (HR). Both received two cycles of OEPA (oncocristine/etoposide/prednisolone/adriamycin). Those in ERA‐CR received two cycles of ABVD if LR, and two and four cycles of COPDac (cyclophosphamide/oncocristine/prednisolone/dacarbazine), respectively, for IR and HR. Involved‐field radiotherapy (IFRT) was given to bulky sites and ERA < CR. Those at LRA < CR (Deauville < 3) or progression at any stage received salvage regimens.ResultsIn the study period, 126 patients were identified who received the above protocol. There were 12 LR, and 114 advanced staged Hodgkin lymphoma (AHL) (18, IR; 96, HR) of which 91 (79.8%) had bulky sites. Eight (66.6%) LR and 93 (83%) AHL patients achieved ERA‐CRs. IFRT was given to 4 (33.3%) LR patients with ERA < CR, and 92 (80.7%) of AHL (91 bulky sites; 1 ERA < CR). At a median follow‐up of 31 months (range, 17–62), three‐year event‐free survival (EFS) and overall survival (OS) were both 100% for LR, and 94.4% (95% CI, 66.0%–99.2%) for IR, whereas for HR it was 90.3% (95% CI, 82.2%–94.8%) and 92.6% (95% CI, 85.2%–96.4%), respectively.ConclusionsChildren with HL have favorable outcomes with manageable toxicities when treated on a risk‐stratified and adapted approach. A high proportion of AHL have bulky disease necessitating IFRT, a concern that will have to be factored in future strategies.

We report a unique case of primary extradural angiosarcoma of posterior fossa manifesting as extradural haematoma in a 12-year-old boy who presented with acute onset headache, vomiting, nuchal rigidity and altered sensorium. The patient underwent a retromastoid suboccipital craniotomy on emergency basis, and the lesion was excised completely. Histopathology and immunohistochemistry revealed an angiosarcoma, following which radiation therapy was given. The patient showed complete clinical and neurological improvement. At a follow-up of 2 years he is in good health without any sign of regrowth.

CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) is a recently described, rare neuroinflammatory disorder diagnosed by clinical symptoms involving the brain stem with a distinct pattern on neuroimaging and a perivascular T-lymphocyte infiltrate on brain biopsy. It is a condition usually described in adults in the fourth to fifth decade. We report a case of 13-year-old Indian boy who presented with recurrent episodes of ataxia and diplopia with onset at 7 years of age. He was investigated extensively to rule out infective, neoplastic, autoimmune, and demyelinating conditions over a span of 6 years. The diagnosis of CLIPPERS was entertained on the basis of clinico-radio-pathological correlation. Treatment with steroids and steroid-sparing agents, particularly methotrexate, seems to provide a promising outcome. With very few cases in literature so far, reporting of a larger case series with pediatric onset may expand it to CLIPPERS spectrum disorder.

No abstract

be explained by varying levels of implementation of Indian tobacco control act (Cigarettes and Other Tobacco Products Act), differential stake holder involvement and involvement of tobacco control agencies and political commitment across different states. Thus, there is a need of in-depth study of the above mentioned factors across two categories of states (declining and increasing trend) to enumerate the key areas of good practices so that it can be replicated in states across the country.