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BackgroundRelapsed 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.MethodsWe 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.Findings11 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%).InterpretationThe 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.

Aim To demonstrate the role of radiographs and ultrasound (USG) in the diagnosis of calcific tendinitis and periarthritis in the wrist and hand and the efficacy of USG-guided barbotage for its management. Materials and Methods A retrospective chart review was performed in six patients who presented with acute-onset pain in the wrist and hand varying from 3 days to 2 weeks. Four patients had tenderness over pisiform and two patients had pain along the lateral aspect of the wrist and thumb. Radiographs and USG revealed calcific focus corresponding to the site of pain. USG-guided calcific barbotage and injection was performed for the same and pain relief was assessed immediately and through telephonic follow-up at 6 months using subjective satisfaction score. Data were analyzed using Microsoft Excel 2013. Results Four patients with tenderness over pisiform had flexor carpi ulnaris calcific tendinitis and two patients with pain along the lateral aspect of the wrist and thumb had first metacarpophalangeal calcific periarthritis and abductor pollicis brevis calcific tendinitis on radiographs as well as USG. In post-USG-guided calcific barbotage and injection, all patients had significant immediate and 6 months delayed relief in symptoms with excellent satisfaction scores. Conclusion Acute calcific tendinitis/periarthritis is a benign and self-limiting inflammatory condition. Radiographs are extremely helpful in identifying calcific focus. Ultrasonography in experienced hands is the best modality to identify, confirm the symptomatic calcific focus, and perform USG-guided intervention. USG-guided calcific barbotage is the simplest, quickest, and effective way to treat this condition and avoid compromised functional capacity.

ObjectiveExtra Nodal Extension (ENE) assessment in locally advanced head and neck cancers (LAHNCC) treated with concurrent chemo radiotherapy (CCRT) is challenging and hence the American Joint Committee on Cancer (AJCC) N staging. We hypothesized that radiology-based ENE (rENE) may directly impact outcomes in LAHNSCC treated with radical CCRT.Materials and MethodsOpen-label, investigator-initiated, randomized controlled trial (RCT) (2012–2018), which included LAHNSCC planned for CCRT. Patients were randomized 1:1 to radical radiotherapy (66–70 grays) with concurrent weekly cisplatin (30 mg/m2) [cisplatin radiation arm (CRT)] or same schedule of CRT with weekly nimotuzumab (200 mg) [nimotuzumab plus CRT (NCRT)]. A total of 536 patients were accrued and 182 were excluded due to the non-availability of Digital Imaging and Communications in Medicine (DICOM) computed tomography (CT) data. A total of 354 patients were analyzed for rENE. Metastatic nodes were evaluated based on five criteria and further classified as rENE as positive/negative based on three-criteria capsule irregularity with fat stranding, fat invasion, and muscle/vessel invasion. We evaluated the association of rENE and disease-free survival (DFS), loco-regional recurrence-free survival (LRRFS), and overall survival (OS).ResultsA total of 244 (68.9%) patients had radiologically metastatic nodes (rN), out of which 140 (57.3%) had rENE. Distribution of rENE was balanced in the two study groups CRT or NCRT (p-value 0.412). The median follow-up period was 39 months (ranging from 35.5 to 42.8 months). Complete response (CR) was seen in 204 (57.6%); incomplete response (IR), i.e., partial response plus stable disease (PR + SD), in 126 (35.6%); and progressive disease (PD) in 24 (6.8%). rENE-positive group had poor survival compared to rENE-negative group 3-year OS (46.7% vs. 63.6%), poor DFS (48.8% vs. 87%), and LRRFS (39.9% vs. 60.4%). rENE positive had 1.71 times increased risk of IR than rENE negative. Overall stage, site, clinical metastatic node (cN), response, and rENE were the significant factors for predicting OS, DFS, and LRRFS on univariate analysis. After making adjustment on multivariate analysis, rENE was an independent prognostic factor for DFS and trending to be significant for OS.ConclusionPre-treatment rENE is an independent prognostic marker for survival in patients with LAHNSCC treated radically with CCRT that can be used as a potential predictive marker for response to treatment and hence stratify patients into responders vs. non-responders. We propose the mahajan rENE grading system applicable on CT, magnetic resonance imaging, positron emission tomography–contrast-enhanced CT, and ultrasound.