PRRT with Lu-177 DOTATATE in Treatment-Refractory Progressive Meningioma: Initial Experience from a Tertiary-Care Neuro-Oncology Center.

PURPOSE: Refractory and/or recurrent meningiomas have poor outcomes, and the treatment options are limited. Peptide receptor radionuclide therapy (PRRT) has been used in this setting with promising results. We have documented our experience of using intravenous (IV) and intra-arterial (IA) approaches of Lu-177 DOTATATE PRRT. METHODS: Eight patients with relapsed/refractory high-grade meningioma received PRRT with Lu-177 DOTATATE by IV and an IA route. At least 2 cycles were administered. Time to progression was calculated from the first PRRT session to progression. The response was assessed on MRI using RANO criteria, and visual analysis of uptake was done on Ga-68 DOTANOC PET/CT. Post-therapy dosimetry calculations for estimating the absorbed dose were performed. RESULTS: Median time to progression was 8.9 months. One patient showed disease progression, whereas seven patients showed stable disease at 4 weeks following 2 cycles of PRRT. Dosimetric analysis showed higher dose and retention time by IA approach. No significant peri-procedural or PRRT associated toxicity was seen. CONCLUSION: PRRT is a safe and effective therapeutic option for relapsed/refractory meningioma. The IA approach yields better dose delivery and should be routinely practised.

A Retrospective Cohort Study to Evaluate the Outcomes of HIV-Associated High-Grade B-Cell Non-Hodgkin Lymphoma (NHL) Treated with Dose Adjusted EPOCH (+/-R) Regimen.

High-grade B-cell NHL's are more common in seropositive patients. They are biologically different from their seronegative counterparts. We report our analysis on our cohort of patients who were treated with DA-EPOCH(+/-R). We retrospectively analyzed treatment-naïve HIV-associated High-grade B-cell NHL patients (aged ≥ 18) treated with DA-EPOCH(+/-R) regimen from 2011 to 2015. Descriptive statistics were summarized with median and range; survival outcomes were analyzed with Kaplan-Meier method. The cohort comprised of 40 patients [DLBCL(19), Burkitt's Lymphoma(16), High-grade B-Cell Lymphoma-Unclassifiable(09), and Plasmablastic Lymphoma(01)] and the median CD4 + T cell count was 202/mm3. CNS prophylaxis was administered with intrathecal methotrexate to 90% of patients. With a median follow-up of 72 months, an estimated 5-year OS was 82.5%, and 5-PFS was 77.5%. There were 9 deaths, and 9 patients had progression. At least 4 cycles of chemotherapy were administered to 35 (93%) patients, with 28 (70%) receiving 6 cycles. Grade 3-4 toxicities were seen in 33 (83%) patients- febrile neutropenia (65%) being the most common followed by mucositis (25%) and peripheral neuropathy (13%). There was no difference in survival based on IPI, CD 4 + T cell count, CDI, or duration of HIV. DA-EPOCH(+/-R) is a highly effective regimen in seropositive high-grade B-cell lymphoma, even in the presence of adverse features. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01652-3.

Multitarget Potential Drug Candidates for High-Grade Gliomas Identified by Multiple Reaction Monitoring Coupled with In Silico Drug Repurposing.

High-grade gliomas (HGGs) are extremely aggressive primary brain tumors with high mortality rates. Despite notable progress achieved by clinical research and biomarkers emerging from proteomics studies, efficacious drugs and therapeutic targets are limited. This study used targeted proteomics, in silico molecular docking, and simulation-based drug repurposing to identify potential drug candidates for HGGs. Importantly, we performed multiple reaction monitoring (MRM) on differentially expressed proteins with putative roles in the development and progression of HGGs based on our previous work and the published literature. Furthermore, in silico molecular docking-based drug repurposing was performed with a customized library of FDA-approved drugs to identify multitarget-directed ligands. The top drug candidates such as Pazopanib, Icotinib, Entrectinib, Regorafenib, and Cabozantinib were explored for their drug-likeness properties using the SwissADME. Pazopanib exhibited binding affinities with a maximum number of proteins and was considered for molecular dynamic simulations and cell toxicity assays. HGG cell lines showed enhanced cytotoxicity and cell proliferation inhibition with Pazopanib and Temozolomide combinatorial treatment compared to Temozolomide alone. To the best of our knowledge, this is the first study combining MRM with molecular docking and simulation-based drug repurposing to identify potential drug candidates for HGG. While the present study identified five multitarget-directed potential drug candidates, future clinical studies in larger cohorts are crucial to evaluate the efficacy of these molecular candidates. The research strategy and methodology used in the present study offer new avenues for innovation in drug discovery and development which may prove useful, particularly for cancers with low cure rates.

Intracranial disease in pediatric Hodgkin lymphoma-case report and review of literature.

Central nervous system (CNS) involvement in Hodgkin lymphoma (HL) is an extremely rare presentation with dismal outcomes according to reported literature. An 8-year-old girl presented to us with complaints of on-off fever, right cervical swelling and bilateral ptosis. Positron emission tomography (PET) showed intracranial extra-axial soft tissue masses in right infero-lateral temporal lobe, sella and bilateral parasellar region along with cervical, mediastinal, axillary, abdominal and inguino-pelvic nodes, liver lesions and extensive marrow lesions involving the axial and appendicular skeleton. Histopathology of the cervical lymph node revealed a diagnosis of classical Hodgkin lymphoma. Child received 2 cycles of OEPA and 4 cycles of COPP followed by radiotherapy to bulky cervical lymph nodes and intracranial lesion. The child has been disease-free for 44 months with no neurological sequalae. Intracranial spread is rare in Hodgkin lymphoma and is associated with inferior outcomes. Due to its rarity, there are no specific treatment guidelines for this entity. The choice of ideal chemotherapeutic agents and role of whole-brain radiotherapy needs further evaluation.

Imaging-Based Patterns of Failure following Re-Irradiation for Recurrent/Progressive High-Grade Glioma.

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 <20% of the recurrence volumes were within 95% isodose lines, respectively. RESULTS: Thirty-seven patients were included in the current analysis. A total of 92% of patients had undergone surgery before ReRT, and 84% received chemotherapy. The median time to recurrence was 9 months. Central, marginal, and distant failures were seen in 27 (73%), 4 (11%), and 6 (16%) patients, respectively. None of the patient-, disease-, or treatment-related factors were significantly different across different recurrence patterns. CONCLUSION: Failures are seen predominantly within the high-dose region following ReRT in recurrent/ progressive HGG.

Phase II trial of a novel chemotherapy regimen CVEP (cyclophosphamide, vinblastine, etoposide and prednisolone) for acquired immunodeficiency syndrome (AIDS)-associated lymphomas.

Management of acquired immunodeficiency syndrome (AIDS)-related diffuse large B-cell (DLBCL) and plasmablastic lymphomas (PBL) poses significant challenges. The evidence supports use of dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin) with or without rituximab as first-line therapy. The need for central venous access, growth factors and significant toxicities limits its use in resource-constrained settings. To address these challenges, we have developed a novel regimen, CVEP (cyclophosphamide, vinblastine, etoposide, and prednisolone) based on the pharmacodynamic principles of dose-adjusted EPOCH. This single-centre phase II study evaluated the efficacy and safety of CVEP regimen in patients with de novo systemic AIDS-related DLBCL and PBL. The primary objective was complete response (CR) rates as assessed by positron emission tomography-computed tomography. The secondary objectives were incidence of Grade 3/4 toxicities, toxicities requiring hospitalisation, and disease-free survival. From May 2011 to February 2017, 42 patients were enrolled. At the end of therapy the CR rates were 69% (29/42) in the intention-to-treat population and 80.5% (29/36) in evaluable patients. At a median follow-up of 69 months, the 5-year disease-free survival was 65.3%. Out of 217 cycles administered, febrile neutropenia occurred in 19.3% and hospitalisation was required in 18.3% of cycles. There were two treatment-related deaths. The CVEP regimen is an active and safe regimen for AIDS-related DLBCL and PBL.

Outcomes of COVID-19 and risk factors in patients with cancer.

Patients with cancer are at higher risk for adverse coronavirus disease 2019 (COVID-19) outcomes. Here, we studied 1,253 patients with cancer, who were diagnosed with severe acute respiratory syndrome coronavirus 2 at a tertiary referral cancer center in India. Most patients had mild disease; in our settings, recent cancer therapies did not impact COVID-19 outcomes. Advancing age, smoking history, concurrent comorbidities and palliative intent of treatment were independently associated with severe COVID-19 or death. Thus, our study provides useful insights into cancer management during the COVID-19 pandemic.

Clinical outcomes and prognostic factors in children with B-cell lymphoblastic lymphoma (LBL) treated according to on modified BFM-90 protocol: Experience from a Tertiary cancer care center in India.

Pediatric B-cell lymphoblastic lymphoma (LBL) is a rare entity, and appropriate treatment for pediatric B-cell LBL is not well defined. While intensive ALL type regimens achieve long term survival of 90% across Western co-operative group trials, published data from Asian studies on long term outcomes are scarce. We retrospectively analyzed the data of pediatric B-cell LBL patients treated between January 2010 and December 2017 on a uniform protocol (modified BFM 90). Kaplan-Meier method was used to estimate the survival and Cox regression models to identify prognostic factors. Of 21 patients who received treatment on the modified BFM-90 protocol, 17(81%) were alive in remission, 3(14%) had relapse, and 1(4%) had treatment-related mortality (TRM) while in remission. Two of 3 relapsed patients subsequently expired. With a median follow-up of 66 months (range 6-114), 5-year event free survival (EFS) and overall survival (OS) were 80% (95% CI:71-89%) and 91% (95% CI:85-97%), respectively. While delayed presentation from symptom onset (p=0.030), and partial response at early (D35) interim assessment (p=0.025) had inferior EFS, patients with elevated baseline LDH had a worse OS (p=0.037). Outcomes of pediatric B-cell LBL patients treated on a modified BFM-90 protocol at a single center in India were excellent. In our study, higher disease burden manifested by elevated baseline LDH and delayed presentation (≥3months) and partial interim response portend poorer survival.Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2021.2005725.

Multidisciplinary Management of Medulloblastoma: Consensus, Challenges, and Controversies.

Medulloblastoma is a highly aggressive "small round blue cell tumor" of the posterior fossa predominantly seen in children. Historically aggressive multimodality regimens have achieved encouraging outcomes with the caveat of severe long-term toxicities. The last decade has unleashed a revolution in terms of evolved understanding of this heterogeneous disease entity in terms of molecular biology. Medulloblastoma as of today is grouped into one of four canonical molecular subgroups (WNT, SHH, Group 3, and Group 4) each characterized by different putative cells of origin, characteristic aberrations at the molecular level, radiogenomics, and outcomes. Our understanding continues to grow in this regard. The future promises much in terms of personalized medicine in tailoring therapy to the needs of individual patients based on their clinical and molecular profile in order to maximize individual and population based outcomes at the cost of minimizing toxicity.

Long-Term Clinical Outcomes and Sequelae of Therapy in Early-Stage Orbital Mucosa-Associated Lymphoid Tissue Lymphoma.

INTRODUCTION: Orbital mucosa-associated lymphoid tissue (MALT) lymphoma, which are rare and indolent, often present at an early stage. We report the efficacy and safety outcomes of treatment in these patients. METHODS: We analyzed adult patients with stage IE or IIE orbital MALT lymphoma between 1999 and 2017 treated at our institute. We assessed local control (LC) rates, overall survival (OS), relapse-free survival (RFS) using Kaplan Meier method and the incidence of late toxicities. RESULTS: Seventy patients were analyzed for clinical outcomes. The median age at diagnosis was 52 years (IQR-45-62 years). Radiotherapy was offered to 97% of patients and the dose ranged from 36 to 45 Gy. Chemotherapy was administered in 5(7.1%) patients. Relapse occurred in 8 patients (local: 2, distant: 6). At a median follow-up of 101 months (IQR-47-146 months), the median OS and RFS was not reached. 8-year OS, RFS and LC rates were 96.5%, 88.5%, 96.7% respectively. Univariate analysis showed age ≤60 years and lacrimal involvement significantly correlated with better OS (P = .01 and .04, respectively). Cataract was the most common sequelae observed in 31 patients (44.3%). CONCLUSION: Moderate doses of radiotherapy are curative in early-stage orbital MALT lymphoma with favorable clinical outcomes. Lower doses of radiation can reduce the toxicity further, without compromising efficacy.

Brain FET PET tumor-to-white mater ratio to differentiate recurrence from post-treatment changes in high-grade gliomas.

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.

Outcomes of Patients with Primary Mediastinal B-Cell Lymphoma Treated with Dose Adjusted R-EPOCH Regimen: A Single Centre Experience.

INTRODUCTION: Primary Mediastinal B cell lymphoma (PMBCL) is a biologically and clinically distinct subset of diffuse large B cell lymphoma. We analysed the outcomes of our cohort of PMBCL patients treated with Dose adjusted (DA)-R-EPOCH regimen. PATIENTS AND METHODS: This is a retrospective analysis of consecutive PMBCL patients who received chemotherapy consisting of DA-R-EPOCH with filgrastim support. Survival analysis was done using Kaplan-Meier method. All calculations were performed using SPSS version 20 for windows. RESULTS: A total of 43 consecutive suspected PMBCL patients were reviewed for this study, 6 patients were excluded as diagnosis of PMBCL could not be established. All patients except one (97.3%) received 6 cycles of R-DA-EPOCH regimen. Median age of the patients was 27 years (range 15-58). Bulky disease (> 7 cm) was present in 97% patients and 54% patients had extranodal disease. With a median follow up of 40 months, 3-year overall survival was 80.6% (95% CI: 74.0-87.2). The 3-year event free survival was 78.4% (95% CI: 71.6-85.2). There were 6 (16.2%) relapses, 1 (2.7%) primary progression and 7 (23%) deaths. Mediastinal radiotherapy was administered to 17 (45.9%) patients. All the deaths were due to disease progression. Grade III/IV toxicities were seen in 28 (75.7%) patients, febrile neutropenia being the most common one. CONCLUSIONS: DA-R-EPOCH regimen is an effective and tolerable regimen in PMBCL patients even with adverse features.

MiR-592 activates the mTOR kinase, ERK1/ERK2 kinase signaling and imparts neuronal differentiation signature characteristic of Group 4 medulloblastoma.

Medulloblastoma, a common malignant brain tumor in children, consists of four molecular subgroups WNT, SHH, Group 3 and Group 4. Group 3, Group 4 tumors have an overlap in their expression profiles and genetic alterations but differ significantly in their clinical characteristics, with Group 3 having the worst 5-year overall survival of <60%. MiR-592 is overexpressed predominantly in Group 4 tumors. MiR-592 expression reduced the anchorage-independent growth, invasion potential and tumorigenicity of Group 3 medulloblastoma cells. DEPTOR, an endogenous inhibitor of the mTOR kinase, and EML1 were identified as novel targets of miR-592. The miR-592 mediated decrease in the DEPTOR expression levels activated both mTORC1 and mTORC2 complex in medulloblastoma cells. However, the miR-592 expression also decreased the AKT kinase activity, likely to be due to the activation of the inhibitory feedback of the mTOR signaling. MiR-592 expression upregulated several neuronal differentiation-related genes, a characteristic of Group 4 medulloblastoma in Group 3 cell lines. The expression of miR-592 also upregulated the activity of ERK1/ERK2 kinases indicating activation of the MAPK signaling pathway. The inhibition of MAPK signaling by the ERK1/ERK2 inhibitor and mTOR signaling by rapamycin abrogated the miR-592-mediated upregulation of neuronal differentiation-related genes. Group 4 medulloblastomas showed higher activity of the mTOR and MAPK signaling compared to Group 3 tumors. Thus, miR-592 overexpression appears to be a driver event and a determining factor of Group 4 biology, which activates the mTOR and MAPK signaling pathways and thereby imparts its characteristic expression profile of neuronal differentiation-related genes.

Prognostic significance of 18F-FDG PET/CT parameters in IDH-1 wild-type GBM and correlation with molecular markers.

AIM: To assess the prognostic role of metabolic parameters on 18F-FDG PET/CT & correlation with molecular markers in IDH-1 wild-type GBM. METHODS: A total of 129 patients with brain lesions showing equivocal findings on baseline MRI who were referred for fluoro-deoxy-glucose PET/CT were analyzed. Of these, 50 underwent surgery/biopsy and postoperative histopathological diagnosis of IDH-1 wild-type GBM. SUVmax, metabolic tumor volume (MTV), total lesion glycolysis (TLG) & T/w ratio was calculated. Median metabolic parameters were used for stratification. Overall survival was calculated using Kaplan-Meier method and was compared using log rank test. P value < 0.05 was considered significant. Multivariate analysis was done using Cox proportional hazard model. Correlation between metabolic parameters and molecular markers was done using Mann-Whitney U test. RESULTS: Median of SUVmax, T/w ratio, MTV, TLG, 18.3, 2.09, 61, 409. Average overall survival (OS) for T/w ratio >2.08 was 5 months, <2.08 was 18 months (P value 0.001). For MTV >61 was 4 months, <61 was 18 months (P value 0.001). Similarly, for TLG >409 was 5 months while for <409 was 19 months (P value 0.001). SUVmax was not significant for OS. In multivariate analysis, age was the statistically significant independent prognostic factor. CONCLUSION: Metabolic parameters of fluoro-deoxy-glucose PET/CT help in prognosticating IDH-1 wild-type GBM. Higher MiB-1 index correlates with higher T/w ratio and is associated with poor overall survival.

Downregulation of ARID1B, a tumor suppressor in the WNT subgroup medulloblastoma, activates multiple oncogenic signaling pathways.

Medulloblastoma, a common pediatric malignant brain tumor, consists of four distinct molecular subgroups WNT, SHH, Group 3 and Group 4. Exome sequencing of 11 WNT subgroup medulloblastomas from an Indian cohort identified mutations in several chromatin modifier genes, including genes of the mammalian SWI/SNF complex. The genome of WNT subgroup tumors is known to be stable except for monosomy 6. Two tumors, having monosomy 6, carried a loss of function mutation in the ARID1B gene located on chromosome 6. ARID1B expression is also lower in the WNT subgroup tumors compared to other subgroups and normal cerebellar tissues that could result in haploinsufficiency. The short hairpin RNA-mediated knockdown of ARID1B expression resulted in a significant increase in the malignant potential of medulloblastoma cells. Transcriptome sequencing identified upregulation of several genes encoding cell adhesion proteins, matrix metalloproteases indicating the epithelial-mesenchymal transition. The ARID1B knockdown also upregulated ERK1/ERK2 and PI3K/AKT signaling with a decrease in the expression of several negative regulators of these pathways. The expression of negative regulators of the WNT signaling like TLE1, MDFI, GPX3, ALX4, DLC1, MEST decreased upon ARID1B knockdown resulting in the activation of the canonical WNT signaling pathway. Synthetic lethality has been reported between SWI/SNF complex mutations and EZH2 inhibition, suggesting EZH2 inhibition as a possible therapeutic modality for WNT subgroup medulloblastomas. Thus, the identification of ARID1B as a tumor suppressor and its downregulation resulting in the activation of multiple signaling pathways opens up opportunities for novel therapeutic modalities for the treatment of WNT subgroup medulloblastoma.

Increased toxicities in children with Burkitt lymphoma treated with rituximab: Experience from a tertiary cancer center in India.

BACKGROUND: Even though rituximab has emerged as standard of care for the management of high-risk pediatric Burkitt lymphoma (BL), its safety in children from the low-middle-income countries (LMICs) remains to be proven. We herein report our experience of using rituximab in children with BL. METHODS: All patients diagnosed with BL between January 2015 and December 2017 were treated in a risk-stratified manner with either the modified MCP-842 or modified LMB protocol. Patients with poor response to MCP-842 were switched to the LMB-salvage regimen. In addition, rituximab was given to selected high-risk patients. RESULT: Forty-two (49.4%) of 85 patients with BL received rituximab. The incidence of febrile neutropenia (90.5% vs 67.4%; P = 0.02), pneumonia (38.1% vs 11.6%; P = 0.005), intensive care unit admissions (54.5% vs 17.6%; P = 0.002), and toxic deaths (26.2% vs 9.3%; P = 0.04) was higher among BL patients who received rituximab. Pneumonia was fatal in 11 of 16 (69%) patients who received rituximab. On multivariate analysis, rituximab continued to be significantly associated with toxic deaths ( OR: 11.45 [95% CI: 1.87-70.07; P = 0.008]). The addition of rituximab to intensive chemotherapy resulted in an inferior one-year event-free survival (49.4% ± 8.1% vs 79.3% ± 6.5%; P = 0.025) and one-year overall survival (63.1% ± 8.5% vs 91.8% ± 4.5%; P = 0.007) with no improvement in one-year relapse-free survival (78.3% ± 7.3% vs 83.9% ± 6.0%; P = 0.817). CONCLUSION: Rituximab was associated with increased toxicities and toxic deaths in our patients. The potential immunomodulatory effect of rituximab and increased susceptibility to infections in patients from LMICs have to be carefully considered while choosing this drug in the treatment of BL in resource-constrained settings.

Primary tonsillar tuberculosis masquerading as carcinoma of the tonsil.

Primary tuberculosis (TB) of tonsil is a rare form of extra-pulmonary tuberculosis. Most tonsillar TB cases present with coexistent pulmonary tuberculosis. It can simulate tonsillar malignancy and poses a diagnostic challenge. Histopathological examination is often needed for confirmation. Herein, we report a case of primary tonsillar tuberculosis in a 55-year-old gentleman mimicking carcinoma of the tonsil.

Outcomes of T-lymphoblastic lymphoma treated with pediatric ALL-like protocol.

BACKGROUND: The management of T-lymphoblastic lymphoma (T-LBL) in adults poses uncertainties, including optimal chemotherapy regimen, need for radiotherapy, and the benefit of stem cell transplant. This retrospective case series investigated the efficacy of the pediatric BFM-90 regimen in adult patients and evaluated the role of early response assessment by positron emission tomography with computed tomography (PET-CT) in predicting outcomes. METHODS: Patients aged 15 years or older with T-LBL diagnosed at Tata Memorial Hospital, Mumbai, India were given chemotherapy according to the European BFM-90 protocol (n = 38). The patients were evaluated for early response by interim PET-CT, post-induction and monitored for toxicity and long-term outcomes. RESULTS: Thirty-eight consecutive patients (median age 23.5 years) were analyzed. After a median follow-up of 33.5 (1-77) months, following induction, 35 out of 38 patients (92.1%) had achieved complete response (CR) on PET-CT. Thirty (78.9%) patients treated according to BFM-90 were alive in first remission. Three-year event-free survival for those with CR on PET-CT was 78%, against no survivors for those who remained PET-positive. CONCLUSION: This study demonstrates the feasibility and efficacy of BFM-90 approach in adults with T-LBL. We found an early PET response to be highly predictive of outcome.

Reverse swing-M, phase 1 study of repurposing mebendazole in recurrent high-grade glioma.

BACKGROUND: Relapsed high-grade glioma has dismal outcomes. Mebendazole has shown promising activity against glioma in in-vitro and in-vivo studies. Hence, we undertook a phase 1 study to repurpose mebendazole in the treatment of glioblastoma. METHODS: We conducted a phase 1 study (accelerated titrated design 4) of mebendazole in patients with recurrent glioblastoma (GBM). Patients eligible for re-irradiation were enrolled in arm A1 (radiation with concurrent temozolomide 75 mg/m2 daily during the course of radiation+mebendazole) while patients who were ineligible were enrolled in either arm B1 (CCNU 110 mg/m2 day 1, every 6 weekly + mebendazole) or arm C1 (temozolomide 200 mg/m2 day 1-5, every 4 weekly + mebendazole). The primary endpoint of phase 1 was to identify the MTD of mebendazole in each combination. FINDINGS: 11 patients were enrolled in the whole study. MTD of mebendazole was not reached in arm A1 and C1 and hence the recommended dose for phase 2 was 1600 mg TDS (4800 mg) per day. The MTD of mebendazole in combination with CCNU was 1600 mg TDS (4800 mg) per day and the dose recommended for phase 2 was 800 mg TDS (2400 mg) per day. The three most common adverse events seen in the study were anemia (n = 9, 81.8%), nausea (n = 7, 63.6%), and fatigue (n = 6, 55.5%). INTERPRETATION: The recommended phase 2 dose of mebendazole is 1600 mg TDS with temozolomide and temozolomide-radiation combination while the dose of 800 mg TDS needs to be used with single-agent CCNU.