Ka On Lam

Intravoxel incoherent motion MR imaging: comparison of diffusion and perfusion characteristics between nasopharyngeal carcinoma and post-chemoradiation fibrosis

ObjectivesTo compare the intravoxel incoherent motion (IVIM) diffusion and perfusion characteristics of nasopharyngeal carcinoma (NPC) and post-chemoradiation fibrosis to aid in their differentiation.MethodsFifty-three (64xa0%) patients with newly diagnosed NPC and 30 (36xa0%) patients with biopsy-proven post-chemoradiation fibrosis were recruited into tumour and fibrosis groups respectively. Diffusion-weighted magnetic resonance (MR) imaging was performed using 13 b values (0–1,000xa0s/mm2). Their respective IVIM parameters (D, pure diffusion; f, perfusion fraction; D*, pseudodiffusion coefficient) were obtained.ResultsD and f were significantly lower in NPC (Du2009=u20090.752u2009±u20090.194u2009×u200910-3xa0mm2/s, P <0.001; fu2009=u20090.122u2009±u20090.095, P <0.001) than in fibrosis (Du2009=u20091.423u2009±u20090.364u2009×u200910-3xa0mm2/s; fu2009=u20090.190u2009±u20090.120); while D* was significantly higher in NPC (111.366u2009±u200965.528u2009×u200910-3xa0mm2/s, P <0.001) than in fibrosis (77.468u2009±u200962.168u2009×u200910-3xa0mm2/s). Respective cut-off values with sensitivity, specificity and accuracy were: Du2009=u20091.062u2009×u200910-3xa0mm2/s (100xa0%, 100xa0%, 100xa0%); fu2009=u20090.132 (66.0xa0%, 100xa0%, 78.3xa0%); D*u2009=u200985.283u2009×u200910-3xa0mm2/s (100xa0%, 90.7xa0%, 96.4xa0%).ConclusionNPC and post-chemoradiation fibrosis have distinctive IVIM parameters. IVIM MR imaging is potentially useful in discrimination between NPC and fibrosis.Key Points• New MRI techniques offer greater help in the assessment of nasopharyngeal carcinoma.• Tumour and post-chemoradiation fibrosis have distinctive intravoxel incoherent motion diffusion/perfusion parameters.• Non-invasive IVIM MRI may help differentiate between tumour and fibrosis.• Pure diffusion is a robust independent discriminating factor which improves diagnostic confidence.

Nasopharyngeal carcinoma: comparison of diffusion and perfusion characteristics between different tumour stages using intravoxel incoherent motion MR imaging

AbstractObjectiveTo explore intravoxel incoherent motion (IVIM) characteristics of nasopharyngeal carcinoma (NPC) and relationships with different tumour stages.MethodsWe prospectively recruited 80 patients with newly diagnosed undifferentiated NPC. Diffusion-weighted MR imaging was performed and IVIM parameters (D, pure diffusion; f, perfusion fraction; D*, pseudodiffusion coefficient) were calculated. Patients were stratified into low and high tumour stage groups based on American Joint Committee on Cancer (AJCC) and TNM staging for determination of the predictive powers of IVIM parameters using t test, multiple logistic regression and ROC curve analyses.ResultsD, f and D* were all statistically significantly lower in high-stage groups in AJCC, T and N staging. D, f and D* were all independent predictors of AJCC staging, f and D* were independent predictors of T staging, and D was an independent predictor of N staging. D was most powerful for AJCC and N staging, whereas f was most powerful for T staging. Optimal cut-off values (area under the curve, sensitivity, specificity, positive likelihood ratio, negative likelihood ratio) were as follows: AJCC stage, Du2009=u20090.782u2009×u200910−3xa0mm2/s (0.915, 93.3xa0%, 76.2xa0%, 3.92, 0.09); T staging, fu2009=u20090.133 (0.905, 80.5xa0%, 92.5xa0%, 10.73, 0.21); N staging, Du2009=u20090.761u2009×u200910−3xa0mm2/s (0.848, 87.5xa0%, 66.7xa0%, 2.62, 0.19). Multivariate analysis showed no diagnostic improvement.ConclusionNasopharyngeal carcinoma has distinctive intravoxel incoherent motion characteristics parameters in different tumour staging, potentially helping pretreatment staging.Key Points• Magnetic resonance imaging is increasingly used to assess nasopharyngeal carcinoma (NPC).n • NPC has distinctive diffusion/perfusion characteristics at different stages.n • Non-invasive MR imaging may help pretreatment staging prediction.n • Diffusion properties of NPC best correlate with AJCC and N staging.n • Perfusion properties of NPC best correlate with T staging.

Intravoxel water diffusion heterogeneity MR imaging of nasopharyngeal carcinoma using stretched exponential diffusion model

AbstractPurposeTo determine the utility of stretched exponential diffusion model in characterisation of the water diffusion heterogeneity in different tumour stages of nasopharyngeal carcinoma (NPC).Materials and methodsFifty patients with newly diagnosed NPC were prospectively recruited. Diffusion-weighted MR imaging was performed using five b values (0–2,500xa0s/mm2). Respective stretched exponential parameters (DDC, distributed diffusion coefficient; and alpha (α), water heterogeneity) were calculated. Patients were stratified into low and high tumour stage groups based on the American Joint Committee on Cancer (AJCC) staging for determination of the predictive powers of DDC and α using t test and ROC curve analyses.ResultsThe meanu2009±u2009standard deviation values were DDCu2009=u20090.692u2009±u20090.199 (×10−3xa0mm2/s) for low stage group vs 0.794u2009±u20090.253 (×10−3xa0mm2/s) for high stage group; αu2009=u20090.792u2009±u20090.145 for low stage group vs 0.698u2009±u20090.155 for high stage group. α was significantly lower in the high stage group while DDC was negatively correlated. DDC and α were both reliable independent predictors (pu2009<u20090.001), with α being more powerful. Optimal cut-off values were (sensitivity, specificity, positive likelihood ratio, negative likelihood ratio) DDCu2009=u20090.692u2009×u200910−3xa0mm2/s (94.4xa0%, 64.3xa0%, 2.64, 0.09), αu2009=u20090.720 (72.2xa0%, 100xa0%, −, 0.28).ConclusionThe heterogeneity index α is robust and can potentially help in staging and grading prediction in NPC.Key Points• Stretched exponential diffusion models can help in tissue characterisation in nasopharyngeal carcinoman • α and distributed diffusion coefficient (DDC) are negatively correlatedn • α is a robust heterogeneity index markern • α can potentially help in staging and grading prediction

Bevacizumab-containing regimens after cetuximab failure in Kras wild-type metastatic colorectal carcinoma

Bevacizumab and cetuximab both improve treatment efficacy when administered with chemotherapy for metastatic colorectal carcinoma (mCRC). Cetuximab has enhanced efficacy in Kras wild-type tumors. However, inferior outcomes have been demonstrated concerning the concurrent use of bevacizumab and cetuximab with chemotherapy. There is an urgent need to define the optimal sequence of use of these two agents. With regard to the pre-clinical data that increased VEGF expression is associated with acquired resistance to anti-EGFR antibody, we performed a retrospective analysis on the outcomes of patients who received bevacizumab-containing regimens after cetuximab failure in Kras wild-type mCRC. From January 2006 to December 2011, patients who received bevacizumab-containing regimens for mCRC in our institution were reviewed. Patients were eligible for further analysis if the following criteria were met: i) Kras wild-type mCRC; ii) chemotherapy and cetuximab received as immediate prior treatment; iii) chemotherapy and bevacizumab received as the index line of treatment; and iv) imaging conducted for response evaluation. Outcome measures included median progression-free survival (mPFS) and objective response rate (ORR). Targeted adverse events were recorded in accordance with two prospective observational cohort studies; the BRiTE and BEAT studies. Fifty patients who received bevacizumab-containing regimens were reviewed and 18 of them met the criteria for further analysis. After a median follow-up of 12.1 months, the mPFS for the total group of patients was 26.3 weeks (95% CI, 19.5–33.0 weeks) with an ORR of 38.9%. Two patients (11.1%) had hypertension that required additional anti-hypertensive drugs and one patient did not survive due to a bowel perforation. No arterial thromboembolic events (ATEs), post-operative wound-healing complications (POWHCs) or grade III/IV bleeding were observed. In patients with Kras wild-type mCRC, bevacizumab-containing regimens following cetuximab failure have modest activity and manageable toxicity.

Intravoxel incoherent motion MR imaging in nasopharyngeal carcinoma: comparison and correlation with dynamic contrast enhanced MR imaging

Objectives To compare accuracy and assess agreement between intravoxel incoherent motion (IVIM) magnetic resonance (MR) perfusion-related parameters and quantitative dynamic contrast-enhanced (DCE) MR parameters in nasopharyngeal carcinoma (NPC). Results D, f, D*, Ktrans, Kep and Vp were significantly lower in the high stage group while Ve was significantly higher in the high stage group. Optimal cut-off values were: D=0.749 × 10−3 mm2/s; f=0.145; D*=100.401 × 10−3 mm2/s; Ktrans=0.571/min; Kep=0.8196/min; Ve=0.6556 %; Vp=0.0757 %. D* (p=0.001), Ktrans (p<0.001), Ve (p=0.014) were all reliable independent predictors for AJCC staging. IVIM-MR perfusion-related (f, D*) and DCE-MR (Ktrans, Kep, Ve, Vp) parameters were significantly correlated (p<0.001). Materials and Methods 75 patients with newly diagnosed NPC were prospectively recruited. Diffusion-weighted MR and DCE-MR imaging were performed with respective IVIM (D, f, D*) and DCE (Ktrans, Kep, Ve, Vp) MR parameters calculated. Patients were stratified into low and high tumor stage groups according to American Joint Committee on Cancer (AJCC) staging for determination of the predictive powers of IVIM-MR and DCE-MR parameters using t–test, ROC curve analyses and multiple logistic regression analysis. Correlation between IVIM-MR perfusion-related and DCE-MR parameters was assessed using Spearmans rank correlation. Conclusion IVIM-MR perfusion-related and quantitative DCE-MR parameters were significantly correlated in the assessment of NPC and were both reliable independent predictors in the prediction of AJCC staging. IVIM-MR perfusion imaging can be a potential useful non-invasive perfusion imaging tool for clinical use in the assessment of NPC.

Radiotherapy for Esophageal Adenocarcinoma

Adenocarcinomas occur in distal esophagus and often involve esophagogastric junction. Radiotherapy plays a key role in treatment, often in combination with chemotherapy and surgery in multi-modalities management. For resectable esophageal primaries, neoadjuvant chemoradiotherapy plus surgery can downstage disease and improve outcome over surgery alone. For patients with unresectable primaries or medically unfit for surgery, definitive chemoradiotherapy was found to improve survival over radiotherapy alone. For patients who had residual disease or involved margins after primary surgery, adjuvant chemoradiotherapy in postoperative setting was shown to improve local control and survival. Palliative radiotherapy can also be used to relieve local symptoms like dysphagia or bleeding. Careful radiotherapy planning is required to ensure adequate dose to target volumes without overdose to normal organs.

A Comprehensive Human Gastric Cancer Organoid Biobank Captures Tumor Subtype Heterogeneity and Enables Therapeutic Screening

Gastric cancer displays marked molecular heterogeneity with aggressive behavior and treatment resistance. Therefore, good inxa0vitro models that encompass unique subtypes are urgently needed for precision medicine development. Here, we have established a primary gastric cancer organoid (GCO) biobank that comprises normal, dysplastic, cancer, and lymph node metastases (nxa0= 63) from 34 patients, including detailed whole-exome and transcriptome analysis. The cohort encompasses most known molecular subtypes (including EBV, MSI, intestinal/CIN, and diffuse/GS, with CLDN18-ARHGAP6 or CTNND1-ARHGAP26 fusions or RHOA mutations), capturing regional heterogeneity and subclonal architecture, while their morphology, transcriptome, and genomic profiles remain closely similar to inxa0vivo tumors, even after long-term culture. Large-scale drug screening revealed sensitivity to unexpected drugs that were recently approved or in clinical trials, including Napabucasin, Abemaciclib, and the ATR inhibitor VE-822. Overall, this new GCO biobank, with linked genomic data, provides a useful resource for studying both cancer cell biology and precision cancer therapy.