Diagnosis of Cholangiocarcinoma (CCA) is difficult, thus a noninvasive approach towards (i) assessing and (ii) monitoring the tumor-specific mutational profile is desirable to improve diagnosis and tailor treatment. Tumor tissue and corresponding ctDNA samples were collected from patients with CCA prior to and during chemotherapy and were subjected to deep sequencing of 15 genes frequently mutated in CCA. A set of ctDNA samples was also submitted for 710 gene oncopanel sequencing to identify progression signatures. The blood/tissue concordance was 74% overall and 92% for intrahepatic tumors only. Variant allele frequency (VAF) in ctDNA correlated with tumor load and in the group of intrahepatic CCA with PFS. 63% of therapy naive patients had their mutational profile changed during chemotherapy. A set of 76 potential progression driver genes was identified among 710 candidates. The molecular landscape of CCA is accessible via ctDNA. This could be helpful to facilitate diagnosis and personalize and adapt therapeutic strategies.

• MRI texture analysis may assist in differentiating low-grade chondrosarcoma from enchondroma. • Kurtosis in the contrast-enhanced T1w has the highest power of discrimination. • Tools provide insight into tumour characterisation as a non-invasive imaging biomarker.

No abstract

PurposePrecision medicine in pancreatic ductal adenocarcinoma (PDAC) could be substantially supported by tools that allow to establish and monitor the molecular setup of the tumor. In particular, noninvasive approaches are desirable, but not validated. Characterization of circulating tumor DNA (ctDNA) may help to achieve this goal.Experimental DesignBlood samples from patients with metastatic PDAC prior to and during palliative treatment were collected. ctDNA and corresponding tumor tissue were analyzed by targeted next generation sequencing and droplet digital PCR for the 7 most frequently mutated genes in PDAC (TP53, SMAD4, CDKN2A, KRAS, APC, ATM, and FBXW7). Findings were correlated with clinical and imaging data.ResultsA total of 20 patients (therapy naïve n = 11; pretreated n = 9) were included. All therapy naïve patients (n = 11/11) presented with detectable ctDNA at baseline. In pretreated patients, 3/7 (prior to 2nd line treatment) and 2/2 (prior to 3rd line chemotherapy) had detectable ctDNA. The combined mutational allele frequency (CMAF) of KRAS and TP53 was chosen to reflect the amount of ctDNA. The median CMAF level significantly decreased during treatment (P = 0.0027) and increased at progression (P = 0.0104). CA19-9 analyses did not show significant differences. In treatment naïve patients, the CMAF levels during therapy significantly correlated with progression-free survival (Spearman, r = −0.8609, P = 0.0013).ConclusionsMonitoring of ctDNA and its changes during treatment may enable to adapt therapeutic strategies to the specific molecular changes present at a certain time during treatment of mPDAC.

Currently available data on prognostic implication of additional neoplasms in GIST miss comprehensive information on patient outcome with regard to overall or disease specific and disease free survival. Registry data of GIST patients with and without additional neoplasm were compared in retrospective case series. We investigated a total of 836 patients from the multi-center Ulmer GIST registry. Additionally, a second cohort encompassing 143 consecutively recruited patients of a single oncology center were analyzed. The frequency of additional malignant neoplasms in GIST patients was 31.9% and 42.0% in both cohorts with a mean follow-up time of 54 and 65 months (median 48 and 60 months), respectively. The spectrum of additional neoplasms in both cohorts encompasses gastrointestinal tumors (43.5%), uro-genital and breast cancers (34.1%), hematological malignancies (7.3%), skin cancer (7.3%) and others. Additional neoplasms have had a significant impact on patient outcome. The five year overall survival in GIST with additional malignant neoplasms (n = 267) was 62.8% compared to 83.4% in patients without other tumors (n = 569) (P < .001, HR=0.397, 95% CI: 0.298-0.530). Five-year disease specific survival was not different between both groups (90.8% versus 90.9%). 34.2% of all deaths (n = 66 of n = 193) were GIST-related. The presented data suggest a close association between the duration of follow-up and the rate of additional malignancies in GIST patients. Moreover the data indicate a strong impact of additional malignant neoplasms in GIST on patient outcome. A comprehensive follow-up strategy of GIST patients appears to be warranted.

This study was conducted to evaluate whether instillation of NaCl 0.9% solution into the biopsy track reduces the incidence of pneumothoraces after CT-guided lung biopsy. A total of 140 consecutive patients with pulmonary lesions were included in this prospective study. All patients were alternatingly assigned to one of two groups: group A in whom the puncture access was sealed by instillation of NaCl 0.9% solution during extraction of the guide needle (n = 70) or group B for whom no sealing was performed (n = 70). CT-guided biopsy was performed with a 18-G coaxial system. Localization of lesion (pleural, peripheral, central), lesion size, needle-pleural angle, rate of pneumothorax and alveolar hemorrhage were evaluated. In group A, the incidence of pneumothorax was lower compared to group B (8%, 6/70 patients vs. 34%, 24/70 patients; P < 0.001). All pneumothoraces occurred directly post punctionem after extraction of the guide needle. One patient in group A and eight patients in group B developed large pneumothoraces requiring chest tube placement (P = 0.01). The frequency of pneumothorax was independent of other variables. After CT-guided biopsy, instillation of NaCl 0.9% solution into the puncture access during extraction of the needle significantly reduces the incidence of pneumothorax.

Treatment of metastatic colorectal cancer (CRC) has continuously improved over the last decade. However, disease monitoring remains underdeveloped and mostly dependent on imaging e.g. RECIST 1.1 criteria. The genetic landscape of individual cancers and subsequently occurring treatment-induced evolution remain neglected in current surveillance strategies. Novel biomarkers demand minimally invasive and repetitive tracking of the cancer mutagenome for therapy stratification and to make prognostic predictions. Carcinoembryonic antigen (CEA), a routinely used tumor marker for CRC, does not meet these goals and thus prevents its use as a reliable monitoring tool. A tumor-derived fraction of circulating cell-free DNA (cfDNA), isolated from blood samples, may bypass the limitations of currently available biomarkers and could be a tool for noninvasive disease monitoring. Here, total cfDNA levels differentiated a cohort of metastatic CRC patients from healthy controls. Furthermore, we correlated cfDNA during chemotherapy of 27 stage IV patients with clinical parameters to establish its prognostic and predictive value. Indeed, cfDNA levels in chemotherapy naive patients correlate with the tumor burden and CEA values at diagnosis and increase upon disease progression during 1st and 2nd line treatment. Moreover, we confirm the possibility of cfDNA-based genotyping of KRAS to early detect the emergence of resistance during chemotherapy. These data indicate that repetitive quantitative and mutational analysis of cfDNA might complement current treatment standards but may have also limited value in some patients.

No abstract