Long-Term 5-Year Response to Pembrolizumab, Bevacizumab, and Capecitabine Regimen in a Metastatic Colon Cancer Patient with MSI-High and KRAS Mutation: Case Report.

With an estimated 1.88 million new cases and 0.92 million deaths in 2020, colorectal cancer accounts for nearly one-tenth of all new cancer and cancer-related deaths worldwide. Nearly half of the patients of colorectal cancer are diagnosed with metastatic or inoperable disease with a very dismal 5-year survival rate. Chemotherapy, targeted therapy, and immunotherapy have been used to treat metastatic disease, either alone or in combination. We present a case of recurrent metastatic colon carcinoma with KRAS exon 2 mutation and high microsatellite instability that was treated with a combination regimen of bevacizumab, capecitabine oral chemotherapy, and pembrolizumab immunotherapy. At nearly 5 years of treatment, the patient is alive with good performance status and improved quality of life owing to a favorable response to the molecular profiling-based treatment approach.

Hypo-fractionated accelerated radiotherapy with concurrent and maintenance temozolomide in newly diagnosed glioblastoma: updated results from phase II HART-GBM trial.

BACKGROUND: Glioblastoma (GBM) patients have poor survival outcomes despite treatment advances and most recurrences occur within the radiation field. Survival outcomes after dose escalation through hypofractionated accelerated RT(HART) were evaluated in this study. We previously reported the study's initial results showing similar survival outcomes with acceptable toxicities. Updated results after 5 years are being analysed to determine long-term survival trends. PATIENTS AND METHODS: 89 patients of newly diagnosed GBM after surgery were randomized to conventional radiotherapy (CRT) or HART. CRT arm received adjuvant RT 60 Gy in 30 fractions over 6 weeks and the HART arm received 60 Gy in 20 fractions over 4 weeks, both with concurrent and adjuvant temozolomide. RESULTS: 83 patients were eligible for analysis. After a median follow-up of 18.9 months, the median OS was 26.5 months and 22.4 months in the HART and CRT arms respectively. 5 year OS was 18.4% in the HART arm versus 3.8% in the CRT arm. This numerical difference in overall survival between the two arms was not statistically significant. The median PFS was not significantly different. CONCLUSION: The long-term results of the trial support HART as a promising treatment option with comparable survival outcomes to the current standard of care. Phase III trials are required for further validation of this regimen which has the potential to become the new standard of care in GBM.

Personalized Treatment Approach to Metastatic Castration-Resistant Prostate Cancer with BRCA2 and PTEN Mutations: A Case Report.

DNA repair mutations (BRCA1 and BRCA2) are found in metastatic castration-resistant prostate cancer (CRPC) patients. Here, we report a case of a 71-year-old male patient with metastatic CRPC along with BRCA2 and PTEN mutations. As per the genomic findings of the Foundation One report, FDA-approved therapies were available for other tumor types, such as olaparib for the loss of BRCA2 and everolimus for the loss of PTEN exons 2-9. These findings were confirmed in another novel phenotypic assay that revealed the sensitivity of olaparib and carboplatin combination therapy. After 4 cycles, our patient achieved a partial response along with a good performance status.

Dual partial arc volumetric-modulated arc therapy: The game changer for accelerated hypofractionated whole-breast radiotherapy with simultaneous integrated tumor cavity boost in early breast cancer - A comparative dosimetric study with single partial arc volumetric-modulated arc therapy.

INTRODUCTION: In a previous study, we demonstrated clinical and dosimetric feasibility of single partial arc volumetric modulated arc therapy (VMAT) for accelerated hypofractionated whole breast radiotherapy with simultaneous integrated boost (SIB) to lumpectomy cavity for early breast cancer. In this dosimetric study, we compared dual partial arcs versus single arc. PATIENTS AND METHODS: Fifteen consecutive patients for treatment with hypofractionated accelerated radiotherapy with SIB using VMAT were planned with single partial arc in an earlier study, initial result of which is published elsewhere. The comparative dosimetric plan was created using two partial arcs. Skewness and kurtosis test, Paired Student's t-test, and Wilcoxon signed-rank test were applied for statistical analysis. P < 0.05 was considered statistically significant. RESULTS: Most planning targets are better achieved with dual arc technique. Coverage of planning target volume (PTV) whole breast (PTVWB) and PTV lumpectomy cavity (PTVBOOST) was significantly improved with dual partial arc without significant difference in conformity index and homogeneity index. Dual arc improved dosimetric parameter significantly. Mean dose (Dmean) and maximum dose (Dmax) of whole breast PTV as well as Dmax of PTVBOOST; ipsilateral and contralateral lung Dmean, Dmax, 5 Gy volume (V5); contralateral lung Dmean, Dmax, V5; Heart V25 and V18; Dmean of 5 mm thickness skin; Dmean and Dmax of ribs; and Dmean and Dmax of contralateral breast were improved with dual arc. CONCLUSION: This is first of its kind study establishing the advantage of dual partial arcs in the current context. Dual partial arcs improved dosimetry over single partial arc. Significant dose reduction can be achieved for multiple crucial organs at risk.

Primary thyroid lymphoma: A series from a tertiary care center in Northern India.

OBJECTIVE: Primary thyroid lymphoma (PTL) is a rare entity, necessitating accurate and early diagnosis, as its management is very different from that of other neoplasms intrinsic to the thyroid. MATERIALS AND METHODS: Cases diagnosed between January 2009 and March 2015 were retrieved, and clinical details were noted. Hematoxylin- and eosin-stained slides were reviewed. Immunohistochemistry (IHC) was performed for immunophenotyping, and cases were classified according to the World Health Organization 2017 classification of hematolymphoid neoplasms. RESULTS: Eleven patients with PTL were identified, with a mean age of 64.6 years (range: 40-76 years), including three males and eight females. Duration of symptoms ranged from 2 to 36 months (mean: 9.3 months). Diffuse large B-cell lymphoma (DLBCL) was most frequent, followed by extranodal marginal zone lymphoma. Most DLBCLs were nongerminal center type. BCL2 was positive in all DLBCLs. Strong p53 immunopositivity was not seen in any of the cases analyzed. CONCLUSION: Histopathological evaluation supplemented by IHC is the gold standard for the diagnosis of PTL. Combined chemoradiotherapy appears to be the best treatment modality, irrespective of histological type. MIB-1 and MUM1 IHC may have a role in identifying DLBCL, particularly in small biopsies. Role of p53 and BCL2 needs further evaluation.

Synchronous orbital and mandibular metastases from squamous cell carcinoma of lung as initial disease presentation in a young female: First report of a rare occurrence.

Metastatic tumor to orbit or mandible as initial presentation is rare. According to the available literature, majority of these described cases had its origin from lung and breast. Adenocarcinoma is the most commonly described histology. Concurrence of both of these metastases from a squamous cell carcinoma of the lung has not been reported in literature as initial presenting symptom. A young female patient with synchronous orbital and mandibular metastases as initial presentation of squamous cell carcinoma of the lung is being presented. The patient was treated with palliative radiation and chemotherapy but unfortunately died of progressive disease. To the best our knowledge, this is the first report describing such unusual presentation.

Hypofractionated accelerated radiotherapy (HART) with concurrent and adjuvant temozolomide in newly diagnosed glioblastoma: a phase II randomized trial (HART-GBM trial).

INTRODUCTION: Maximal safe surgical resection followed by adjuvant chemoradiation has been standard for newly diagnosed glioblastoma multiforme (GBM). Hypofractionated accelerated radiotherapy (HART) has the potential to improve outcome as it reduces the overall treatment time and increases the biological effective dose. METHODS: Between October 2011 and July 2017, a total of 89 newly diagnosed GBM patients were randomized to conventional fractionated radiotherapy (CRT) or HART. Radiotherapy was delivered in all patients with a three-dimensional conformal radiotherapy technique in CRT arm (60 Gy in 30 fractions over 6 weeks @ 2 Gy/per fraction) or simultaneous integrated boost intensity modulated radiotherapy in HART arm (60 Gy in 20 fractions over 4 weeks @ 3 Gy/per fraction to high-risk planning target volume (PTV) and 50 Gy in 20 fractions over 4 weeks @ 2.5 Gy/per fraction to low-risk PTV). The primary endpoint of the trial was overall survival (OS). RESULTS: After a median follow-up of 11.4 months (Range: 2.9-42.5 months), 26 patients died and 39 patients had progression of the disease. Median OS for the entire cohort was 23.4 months. Median OS in the CRT and HART arms were 18.07 months (95% CI 14.52-NR) and 25.18 months (95% CI 12.89-NR) respectively, p = 0.3. Median progression free survival (PFS) for the entire cohort was 13.5 months (Range: 11.7-15.7 months). In multivariate analysis patients younger than 40 years of age, patients with a gross total resection of tumor and a mutated IDH-1 had significantly better OS. PFS was significantly better for patients with a gross total resection of tumor and a mutated IDH-1. All patients included in the trial completed the planned course of radiation. Only two patients required hospital admission for features of raised intracranial tension. One patient in the HART arm required treatment interruption. CONCLUSION: HART is comparable to CRT in terms of survival outcome. HART arm had no excess treatment interruption and minimal toxicity. Dose escalation, reduction in overall treatment time, is the advantages with use of HART.

Recurrent intracranial Rosai-Dorfman disease: Management of a challenging case.

Rosai-Dorfman disease (RDD) is a rare, idiopathic, benign histioproliferative disorder. Extranodal involvement is seen in around 25-40% of patients. Central nervous system manifestation of RDD is uncommon and suprasellar location of the lesion is a distinct rarity. Surgery is the cornerstone of management of intracranial RDD. However, tumor recurrence or regrowth is a potential problem. Hence, low dose conformal radiotherapy (RT) should be considered in patients undergoing sub-total resection or having unresectable recurrent disease. Though cranial RT usually leads to satisfactory improvement of symptoms and long-term disease stabilization or regression, in few patients there may be an eventual progression of disease for which systemic chemotherapy may be considered. We have highlighted the salient features of this enigmatic disease by citing a case of a 50-year-old male patient with suprasellar RDD treated by maximal safe surgery and deferred radiation therapy on progression.

Comparative Study of Adjuvant Temozolomide Six Cycles Versus Extended 12 Cycles in Newly Diagnosed Glioblastoma Multiforme.

INTRODUCTION: Studies have shown promising survival with the use of Extended Temozolomide (E-TMZ) as compared to Conventional six cycles of Temozolomide (C-TMZ) in malignant gliomas; however, the reports are mostly limited to retrospective studies with significant bias. AIM: This study assesses the impact of six versus 12 cycles of adjuvant Temozolomide (TMZ) on Overall Survival (OS) in newly diagnosed postoperative patients of Glioblastoma Multiforme (GBM). MATERIALS AND METHODS: Between January 2012 and July 2013, 40 postoperative patients of GBM between age 18-65 years and Karnofsky Performance Score (KPS) ≥70 were included. Patients were randomized to receive radiation (60 Gray in 30 fractions over six weeks) with concomitant TMZ (75 mg/m2/day) and adjuvant therapy with either six (C-TMZ arm) or 12 cycles (E-TMZ arm) of TMZ (150-200 mg/m2 for five days, repeated four weekly). Twenty patients were treated in each arm. Toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. OS and Progression Free Survival (PFS) were calculated from the time of diagnosis. Kaplan Meier method was used for survival analysis. A p-value of <0.05 was taken as significant and SPSS version 12.0 was used for all statistical analysis. RESULTS: Median number of adjuvant TMZ cycles was six and 12 in C-TMZ and E-TMZ arm respectively. Overall, 5% and 15% patients respectively in C-TMZ and E-TMZ arm had haematological toxicity ≥ 3 in grade. Median follow up in C-TMZ and E-TMZ arm were 14.65 months and 19.85 months. Median PFS was 12.8 months and 16.8 months in C-TMZ and E-TMZ arm respectively (p=0.069). Median OS was 15.4 months vs. 23.8 months in C-TMZ and E-TMZ arm respectively (p=0.044). CONCLUSION: Our study showed that E-TMZ is well tolerated and leads to a significant increase in PFS as well as OS in newly diagnosed patients of GBM. Further prospective randomized studies are needed to validate the findings of our study.

Indian Council of Medical Research Consensus Document for the Management of Non-Hodgkin's Lymphoma (High Grade).

This consensus document is based on the guidelines related to the management of Non Hodgkin's Lymphoma (High grade) in the Indian population as proposed by the core expert committee. Accurate diagnosis in hematolymphoid neoplasm requires a combination of detailed history,clinical examination, and various investigations including routine laboratory tests, good quality histology section (of tumor and also bone marrow aspirate/biopsy), immunostaining, cytogenetic and molecular studies and radiology investigations. The staging system used for adult high grade lymphomas is based on the Ann Arbor system and includes various parameters like clinical, haematology, biochemistry, serology and radiology. Response should be evaluated with radiological evaluation after 3-4 cycles and at the end of treatment based on criteria including and excluding PET. Treatment of high grade lymphomas is based on histologic subtype, extent of disease, and age of the patient. Autologous stem cell transplantation after high dose chemotherapy is effective in the treatment of relapsed NHL. Newer RT techniques like 3 dimensional conformal radiation therapy (3D-CRT) and intensity modulated radiation therapy (IMRT) can significantly reduce radiation doses to surrounding normal tissues in lymphoma patients. Patients should be followed up every 3 to 4 months for the first 2 years, followed by 6 monthly for the next 3 years and then annually.

Treatment Outcome in Patients with Primary Central Nervous System Germ Cell Tumour: Clinical Experience from a Regional Cancer Centre in North India.

BACKGROUND: Primary intracranial germ cell tumour is a rare entity and constitutes 2-3% of all paediatric brain tumours in Western countries. We herein intend to report the clinical features and treatment outcome of patients with primary central nervous system germ cell tumour treated at our institute. METHODS: Clinical data were collected by retrospective chart review from 2006 to 2012. Histopathology slides were reviewed and relevant immunohistochemistry stains were done. Overall survival (OS) and progression-free survival (PFS) were analysed by the Kaplan-Meier product-limit method. RESULTS: Twenty patients met the study criterion (male:female = 7:3). Median age at presentation was 13 years. Tumour location was pineal in 10 patients, suprasellar in 6, thalamic in 2, basal ganglion in 1, and spinal in 1. Leptomeningeal spread was noted in 1 patient at presentation. Surgical resection was gross-total in 7 patients (35%), near-total in 2 (10%), subtotal in 4 (20%), and limited to biopsy in 6 (30%). The tumours were germinomatous, non-germinomatous, and of mixed germ cell subtype in 17 patients (85%), 2 patients (10%), and 1 patient (5%), respectively. Systemic chemotherapy (median of 4 cycles) was given to 19 patients (95%). The common regimens used were a combination of bleomycin, etoposide and cisplatin (BEP) in 14 patients (70%) and etoposide and cisplatin (EP) in 5 patients (25%). Radiation therapy (40-50 Gy in conventional fractionation; median of 42 Gy) was delivered to 17 patients (85%): local radiation in 6 and whole ventricular, whole brain, and craniospinal irradiation followed by a boost in 5, 3, and 3 patients, respectively. After a median follow-up of 44.52 months, 17 patients (85%) were in complete response and 3 (15%) had progressive disease. Death and disease recurrence were noted in 6 patients (30%) and 1 patient, respectively. Median OS and PFS were not reached. The actuarial rates of OS at 3 and 5 years were 75.8 and 68.9%, respectively. The actuarial rates of PFS at both 3 and 5 years were 81.6%. CONCLUSION: Multimodality treatment consisting of limited resection followed by platinum-based systemic chemotherapy and radiotherapy (40-50 Gy) is a reasonable treatment strategy in patients of primary central nervous system germ cell tumour in a developing nation.

Extent of surgical resection and adjuvant temozolomide improves survival in pediatric GBM: a single center experience.

BACKGROUND: Pediatric glioblastoma (pGBM) is an uncommon entity. The importance of concurrent and adjuvant temozolomide is not known in this subset of patients. METHODS: We retrospectively analyzed our database between 2000 and 2015. All patients were treated with maximally safe surgical resection. This was followed by a uniform treatment schedule of post-operative radiation with concurrent daily temozolomide at 75 mg/m2. Radiation dose was 60 Gy in 30 fractions planned by 3-dimensional conformal radiotherapy. Concurrent and adjuvant temozolomide was used in all patients treated after 2007. Four weeks later, adjuvant temozolomide was started at 150 mg/m2, day 1 to 5 every 28 days and escalated to 200 mg/m2 from the second cycle onwards if well tolerated. Log-rank test was used to compare survival distribution. The data was analyzed using SPSS (version 16). RESULTS: Fifty-one patients were analyzed. Median age was 14 years (range: 5 to 21 years). Thirty-five males and 16 females were noted. Median symptom duration was 4 months. Twenty-eight patients underwent a gross total resection (GTR) while 17 underwent a subtotal resection; six patients underwent decompression. Thirty-three patients received concurrent chemotherapy while 27 received adjuvant chemotherapy. Median progression-free survival (PFS) was 15.1 months. One- and 3-year PFS was 54.4% and 3-year PFS was 24.6.7%. The median overall survival was 17.4 months. In univariate analysis survival was better for gross total resection (17.4 months vs. 11.5 months; p = 0.037), and significance maintained after multivariate analysis p = 0.026, HR 3.069, 95% CI 1.14-8.23. In univariate analysis, survival was better for patients receiving temozolomide but did not achieve significance. However, in multivariate analysis, use of temozolomide was associated with significantly improved survival p = 0.036, HR 3.315, 95% CI 1.07-10.19. CONCLUSIONS: GTR improves survival significantly in pGBM. Adjuvant temozolomide may improve survival in pGBM.

Accelerated hypofractionated adjuvant whole breast radiation with simultaneous integrated boost using volumetric modulated arc therapy for early breast cancer: A phase I/II dosimetric and clinical feasibility study from a tertiary cancer care centre of India.

BACKGROUND: Hypofractionation has become standard of care after Breast Conserving Therapy (BCT) in many European and few others western countries. Though still debatable, tumor cavity boost is routinely practised in our centre. Hypofractionation is not yet the current standard of practice in Asian countries. Employing hypofractionation and simultaneous integrated boost to lumpectomy cavity with conformal technique is not the current practice in this region. Hence the study was performed to see whether accelerated hypofractionation and simultaneous boost can be combined using volumetric modulated arc therapy (VMAT) in treating early breast cancer (EBC) patients. PATIENTS AND METHODS: Female patients with EBC treated by whole breast radiation and boost were treated simultaneously to a dose of 40.5Gy and 48Gy in fifteen fractions over three weeks to entire breast and tumor cavity respectively with VMAT. Dosimetry including target coverage, OAR (organ at risk) sparing and acute radiation toxicity were evaluated. RESULTS: Ten consecutive patients were treated. Planning target volume (PTV) coverage and OAR sparing were mostly satisfactory. Mean volume of PTVWB and PTVBoost were 786.18cm3 and 228.9cm3 respectively. Mean Dmean to PTVWB and PTVBOOST were 41.9Gy and 49.1Gy respectively. Dmax to PTVWB and PTVBOOST were 127.56% and 110.67% respectively. Ipsilateral lung mean dose and V20 were 13.92Gy and 21.53% respectively. V40 and V25 of heart were 0.17% and 2.25% respectively. All patients are disease free after a median follow up of two years. Most acute toxicities were Grade1. Only two patients out of ten developed Grade 2 skin reaction during radiation. Early cosmesis using Harvard cosmesis scale is good to excellent. CONCLUSIONS: Accelerated hypofractionated RT using SIB-VMAT is a clinically feasible technique with acceptable initial result. Initial results are encouraging. MINI ABSTRACT: Simultaneous integrated boost with accelerated hypofractionated whole breast radiotherapy using Volumetric Modulated Arc Therapy is a novel approach. Patient selection and technical considerations are of paramount importance. The present study describes successful implementation of this approach.

Prognostic Factors and Survival Outcomes of Intracranial Ependymoma Treated with Multimodality Approach.

OBJECTIVES: We aimed to analyze treatment outcomes of intracranial ependymoma (ICE) treated at our institute with multimodality approach. MATERIALS AND METHODS: Demography, treatment details, and survival data of 40 patients (2005-2012) were collected in a predesigned pro forma. Kaplan Meier method was used to analyze disease-free survival (DFS) and the impact of prognostic factors was determined using univariate analysis (log-rank test). Multivariate analysis was performed using Cox-proportional hazard model. SPSS version 21.0 was used for all statistical analysis. RESULTS: Male:female ratio was 29:11. Gross total resection: subtotal resection or less was 42.5%: 57.5%. A total of 16 patients (40%) had anaplastic histology. All except two patients received adjuvant radiotherapy. Four patients received concurrent chemotherapy (temozolomide [TMZ]) and 10 patients received adjuvant chemotherapy (6 carboplatin plus etoposide; 4 TMZ). Median follows up was 18 months (2-60 months). Median DFS for the entire cohort was 22.42 months. The estimated 1, 2, and 3 years DFS was found to be 58.5%, 41%, and 30.7%, respectively. On univariate analysis, patients receiving higher radiation dose (56 Gray vs. 60 Gray; hazard ratio [HR] 0.366; 95% confidence interval [CI] 0.142-0.9553; P = 0.02) and lower MIB labeling index (<20 vs. ≥20; HR 0.238; 95% CI 0.092-0.617; P = 0.001) had a better DFS. Higher radiation dose continued to be an independent prognostic factor on multivariate analysis (HR 0.212; 95% CI 0.064-0.856; P = 0.03). CONCLUSION: ICE has guarded prognosis. Adjuvant radiotherapy to a higher radiation dose improves survival. Higher MIB labeling index connotes a dismal survival despite the use of radiotherapy and chemotherapy.

Genome-wide ChIP-seq analysis of EZH2-mediated H3K27me3 target gene profile highlights differences between low- and high-grade astrocytic tumors.

Enhancer of zeste homolog-2(EZH2) is a key epigenetic regulator that functions as oncogene and also known for inducing altered trimethylation of histone at lysine-27 (H3K27me3) mark in various tumors. However, H3K27me3 targets and their precise relationship with gene expression are largely unknown in astrocytic tumors. In this study, we checked EZH2 messenger RNA and protein expression in 90 astrocytic tumors of different grades using quantitative PCR and immunohistochemistry, respectively. Further, genome-wide ChIP-seq analysis for H3K27me3 modification was also performed on 11 glioblastomas (GBMs) and 2 diffuse astrocytoma (DA) samples. Our results showed EZH2 to be highly overexpressed in astrocytic tumors with a significant positive correlation with grade. Interestingly, ChIP-seq mapping revealed distinct differences in genes and pathways targeted by these H3K27me3 modifications between GBM versus DA. Neuroactive ligand receptor pathway was found most enriched in GBM (P = 9.4 × 10-25), whereas DA were found to be enriched in metabolic pathways. Also, GBM showed a higher enrichment of H3K27me3 targets reported in embryonic stem cells and glioma stem cells as compared with DAs. Our results show majority of these H3K27me3 target genes were downregulated, not only due to H3K27me3 modification but also due to concomitant DNA methylation. Further, H3K27me3 modification-associated gene silencing was not restricted to promoter but also present in gene body and transcription start site regions. To the best of our knowledge, this is the first high-resolution genome-wide mapping of H3K27me3 modification in adult astrocytic primary tissue samples of human, highlighting the differences between grades. Interestingly, we identified SLC25A23 as important target of H3K27me3 modification, which was downregulated in GBM and its low expression was associated with poor prognosis in GBMs.

Surviving Triple Trouble: Synchronous Breast and Cervical Cancer, HIV Infection and Myocardial Infarction.

Breast and cervical cancer are the two most common cancers in female. However, owing to the contrasting risk factors, synchronous breast and cervical cancer has very rarely been reported. However, noncommunicable disease like cardiovascular disease and different infections has tended to make situations complicated because of complex interaction. In recent years, such cases are being seen frequently and their management is challenging. We report such a case of synchronous breast and cervical cancer complicated by HIV infection and myocardial infarction. This highlights the importance of a wide spectrum of clinical knowledge and skill and interdisciplinary coordination.

Primary pediatric mid-brain lymphoma: Report of a rare pediatric tumor in a rare location.

Primary central nervous system lymphoma (PCNSL) is a rare disease in pediatric age group. A thirteen-year-old male child presented with complaints of headache for six months, vomiting and diplopia for three days. Magnetic resonance imaging of the brain showed a single lesion of 1.7 cm × 1.6 cm × 1.6 cm in the mid brain and tectum. He underwent a gross total resection of the tumor. The histopathological evaluation revealed B cell high grade non Hodgkin lymphoma. The patient was treated with High dose methotrexate and cranio spinal radiation. The patient was alive without disease 12 mo after completion of treatment. This case highlights importance of keeping PCNSL as differential in brain stem lesions of pediatric patients also. Radiation and chemotherapy remains the most important treatment for such patients.

Atypical teratoid/rhabdoid tumors: challenges and search for solutions.

Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant embryonal central nervous system tumor commonly affecting children <3 years of age. It roughly constitutes 1%-2% of all pediatric central nervous system tumors. Recent data show that it is the most common malignant central nervous system tumor in children <6 months of age. Management of this aggressive tumor is associated with a myriad of diagnostic and therapeutic challenges. On the basis of radiology and histopathology alone, distinction of AT/RT from medulloblastoma or primitive neuroectodermal tumor is difficult, and hence this tumor has been commonly misdiagnosed as primitive neuroectodermal tumor for decades. Presence of a bulky heterogeneous solid-cystic mass with readily visible calcification and intratumor hemorrhage, occurring off-midline in children <3 years of age, should alert the radiologist toward the possibility of AT/RT. Presence of rhabdoid cells on histopathology and polyphenotypic immunopositivity for epithelial, mesenchymal, and neuroectodermal markers along with loss of expression of SMARCB1/INI1 or SMARCA4/BRG1 help in establishing a diagnosis of AT/RT. The optimal management comprises maximal safe resection followed by radiation therapy and multiagent intensive systemic chemotherapy. Gross total excision is difficult to achieve in view of the large tumor size and location and young age at presentation. Leptomeningeal spread is noted in 15%-30% of patients, and hence craniospinal irradiation followed by boost to tumor bed is considered standard in children older than 3 years. However, in younger children, craniospinal irradiation may lead to long-term neurocognitive and neuroendocrine sequel, and hence focal radiation therapy may be a pragmatic approach. In this age group, high-dose chemotherapy with autologous stem cell rescue may also be considered to defer radiation therapy, but this approach is also associated with significant treatment-related morbidity and mortality. Novel small molecule inhibitors hold promise in preclinical studies and should be considered in patients with relapsed or refractory tumor.

Solitary fibrous tumor of the sellar region treated with adjuvant radiation therapy.

The solitary fibrous tumor of central nervous system is rare. Herein, a case of solitary fibrous tumor arising from sellar region is described. A 60-year-old man underwent subtotal excision of the tumor because of extensive infiltration of optical and vascular structures. In view of the presence of residual tumor, he was treated with adjuvant radiation therapy. After a follow-up period of 1 year, there was no progression of the lesion evident on magnetic resonance imaging of the brain. Solitary fibrous tumor should be considered as one of the differential diagnosis of a mass lesion arising in sellar region. Immunohistochemistry with CD34 is valuable for discerning the diagnosis. Complete surgery should be the goal of treatment and adjuvant radiation therapy may be considered for residual or recurrent disease.

Prognostic Stratification of GBMs Using Combinatorial Assessment of IDH1 Mutation, MGMT Promoter Methylation, and TERT Mutation Status: Experience from a Tertiary Care Center in India.

This study aims to establish the best and simplified panel of molecular markers for prognostic stratification of glioblastomas (GBMs). One hundred fourteen cases of GBMs were studied for IDH1, TP53, and TERT mutation by Sanger sequencing; EGFR and PDGFRA amplification by fluorescence in situ hybridization; NF1expression by quantitative real time polymerase chain reaction (qRT-PCR); and MGMT promoter methylation by methylation-specific PCR. IDH1 mutant cases had significantly longer progression-free survival (PFS) and overall survival (OS) as compared to IDH1 wild-type cases. Combinatorial assessment of MGMT and TERT emerged as independent prognostic markers, especially in the IDH1 wild-type GBMs. Thus, within the IDH1 wild-type group, cases with only MGMT methylation (group 1) had the best outcome (median PFS: 83.3 weeks; OS: not reached), whereas GBMs with only TERT mutation (group 3) had the worst outcome (PFS: 19.7 weeks; OS: 32.8 weeks). Cases with both or none of these alterations (group 2) had intermediate prognosis (PFS: 47.6 weeks; OS: 89.2 weeks). Majority of the IDH1 mutant GBMs belonged to group 1 (75%), whereas only 18.7% and 6.2% showed group 2 and 3 signatures, respectively. Interestingly, none of the other genetic alterations were significantly associated with survival in IDH1 mutant or wild-type GBMs. Based on above findings, we recommend assessment of three markers, viz., IDH1, MGMT, and TERT, for GBM prognostication in routine practice. We show for the first time that IDH1 wild-type GBMs which constitute majority of the GBMs can be effectively stratified into three distinct prognostic subgroups based on MGMT and TERT status, irrespective of other genetic alterations.