Use of volumetric CT scanning to predict tumor staging and survival in pancreatic cancer patients that are to be administered curative resection.

BACKGROUND: This study evaluates the achievability of CT volumetry of pancreatic cancer and its correlation with pTNM stage and survival. METHODS: Tumor volume was measured from contrast enhanced CT images of 58 patients who undergo curative resection for pancreatic cancer using the Segment Editor module implemented in 3D-Slicer-a free open source software platform. Receiver operating characteristic (ROC) analysis was used to evaluate correlation between Tvol and pTNM staging. RESULTS: The preoperative images of 58 pancreatic adenocarcinoma patients were included. The mean Tvol of pancreatic cancer is an increasing trend with T stage (The mean T1vol = 1.75 cm3 , the mean T2vol = 11.43 cm3 , the mean T3vol = 14.98 cm3 , the mean T4vol = 19.6 cm3 ). There were statistical differences between volumes (p = .000). On ROC analysis, the area under the ROC curve (Az) of Tvol to differentiate T1 stage from ≥T2 stage was 0.966 (p = .000). At a cut-off value of 3.050 cm3 , sensitivity of 92.3%, and specificity of 83.3% were achieved. Az value of Tvol to differentiate ≤T2 from ≥T3 stage was 0.750 (p = .010). At a cut-off value of 10.250 cm3 , sensitivity of 72.7% and specificity of 66% were achieved. In addition Az value of Tvol to differentiate ≤T3 from ≥T4 stage was 0.652 and was not significant (p = .380). At a cut-off value of 11.2 cm3 , sensitivity of 66.7% and specificity of 63.6% were achieved. CONCLUSION: CT volumetry in pancreatic cancer is feasible with excellent reproducibility. It is one of the prognostic factors affecting survival in operated patients with pancreatic cancer.

Patients with NSCLCs Harboring Internal Inversions or Deletion Rearrangements of the ALK Gene Have Durable Responses to ALK Kinase Inhibitors.

BACKGROUND: ALK fusions are targetable drivers in non-small-cell lung cancer (NSCLC). However, patients with NSCLC harboring ALK rearrangements without a fusion partner identified in DNA have also been shown to respond to ALK inhibitors. We aimed to characterize complex ALK variants that may predict sensitivity to multiple approved ALK inhibitors. METHODS: Comprehensive genomic profiling (CGP) of DNA isolated from formalin-fixed paraffin-embedded (FFPE) tumor tissue or blood-based circulating tumor DNA was performed for 39,159 NSCLC patients during routine clinical care. For a subset of cases, RNA sequencing was performed, and prior ALK test results and clinical treatment information were collected from treating physicians. RESULTS: We queried the Foundation Medicine NSCLC database and identified ALK internal inversions, as well as internal deletions, as the sole ALK rearrangements in 6 (0.02%) and 3 (0.01%) of cases, respectively. In cases with ALK internal inversions, RNA testing identified an EML4-ALK fusion in 2/2 cases evaluated, and 3/3 patients treated with ALK inhibitors had durable responses. A single patient with an ALK internal deletion and clinical data available responded to multiple ALK inhibitors. RNA data available for a subset of non-NSCLC cases suggest that ALK internal deletions removing a portion of the N-terminus are drivers themselves and do not result in ALK fusions. Fluorescence in situ hybridization (FISH) results were inconsistent for both classes of DNA events. CONCLUSION: Rare internal inversions of ALK appear to be indicative of ALK fusions, which can be detected in RNA, and response to ALK inhibitors in patients with NSCLC. In contrast, ALK internal deletions are not associated with ALK fusions in RNA but likely represent targetable drivers themselves. These data suggest that CGP of DNA should be supplemented with immunohistochemistry or RNA-based testing to further resolve these events and match patients to effective therapies.