The reality of cholangiocarcinoma in India– real world data from a tertiary referral centre

BackgroundCholangiocarcinomas (CCA) are rare tumours originating from bile duct. Due to their asymptomatic nature they are usually diagnosed when the disease is advanced. Little data exists with respect to their incidence and treatment outcomes in low and middle income countries.MethodA retrospective analysis of a prospectively maintained database of all patients with perihilar (pCCA) and intrahepatic (iCCA) CCA registered between January 2012 and December 2018 was performed.ResultsA total of 760 patients, 427 (56.2%) diagnosed with pCCA and 333 (43.8%) of iCCA were included. Patients with localised, locally advanced and metastatic disease in pCCA were 45.5%, 25.9%, 8.5% and that in iCCA were 22.1%, 10.1% and 67.7% respectively. Only 141 (43.9%, 57 - iCCA, 84 -pCCA) of the total 321 patients started on some definitive cancer directed therapy could complete the intended treatment. The overall curative resection rate for all patients of iCCA was 14.5% whereas for patients of pCCA it was only 10.5%.ConclusionMore than half of CCA patients are not able to complete their intended treatment, being worse for pCCA as compared to iCCA. Early referral and centralisation of treatment for this complex disease might be the way forward to achieve optimal outcomes.     

Molecular profiling of Chinese R-CHOP treated DLBCL patients: Identifying a high-risk subgroup

Diffuse large B-cell lymphoma (DLBCL) is a clinically aggressive and heterogenous disease. Although most patients can be cured by immunochemotherapy, 30% to 40% patient will ultimately develop relapsed or refractory disease. Here, we investigated the molecular landscapes of patients with diverse responses to R-CHOP. We performed capture-based targeted sequencing on baseline samples of 105 DLBCL patients using a panel consisting of 112 lymphoma-related genes. Subsequently, 81 treatment-naïve patients with measurable disease and followed for over 1 year were included for survival analysis. Collectively, the most commonly seen mutations included IGH fusion (69%), PIM1(33%), MYD88 (29%), BCL2 (29%), TP53 (29%), CD79B (25%) and KMT2D (24%). Patients with TP53 mutations were more likely to have primary refractory disease (87.0% vs 50.0%, P = .009). For those with TP53 disruptive mutations, 91.7% patients were in the primary refractory group. Interestingly, BCL-2 somatic hypermutation was only seen in patients without primary refractory disease (P = .014). In multivariate analysis, BCL-2 amplification (hazard ratio [HR] = 2.94, P = .022), B2M mutation (HR = 2.99, P = .017) and TP53 mutation (HR = 3.19, P < .001) were independently associated with shorter time to progression (TTP). Furthermore, TP53 mutations was correlated with worse overall survival (P = .049). Next, we investigated mutation landscape in patients with wild-type (WT) TP53 (n = 58) and found that patients harboring MYD88 L265P had significantly inferior TTP than those with WT or non-265P (P = .046). Our study reveals the mutation spectrum of treatment-naive Chinese DLBCL patients. It also confirms the clinical significance of TP53 mutations and indicates the prognostic value of MYD88 L265P in TP53 WT patients.