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Circulating tumor cells (CTCs) were introduced as biomarkers more than 10 years ago, but capture of viable CTCs at high purity from peripheral blood of cancer patients is still a major technical challenge. Here, we report a novel microfluidic platform designed for marker independent capture of CTCs. The Parsortix™ cell separation system provides size and deformability‐based enrichment with automated staining for cell identification, and subsequent recovery (harvesting) of cells from the device. Using the Parsortix™ system, average cell capture inside the device ranged between 42% and 70%. Subsequent harvest of cells from the device ranged between 54% and 69% of cells captured. Most importantly, 99% of the isolated tumor cells were viable after processing in spiking experiments as well as after harvesting from patient samples and still functional for downstream molecular analysis as demonstrated by mRNA characterization and array‐based comparative genomic hybridization. Analyzing clinical blood samples from metastatic (n = 20) and nonmetastatic (n = 6) cancer patients in parallel with CellSearch® system, we found that there was no statistically significant difference between the quantitative behavior of the two systems in this set of twenty six paired separations. In conclusion, the epitope independent Parsortix™ system enables the isolation of viable CTCs at a very high purity. Using this system, viable tumor cells are easily accessible and ready for molecular and functional analysis. The system's ability for enumeration and molecular characterization of EpCAM‐negative CTCs will help to broaden research into the mechanisms of cancer as well as facilitating the use of CTCs as “liquid biopsies.”

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Cancer immunotherapy with antibodies targeting immune checkpoints, such as programmed cell death protein 1 (PD-1), shows encouraging results, but reliable biomarkers predicting response to this costly and potentially toxic treatment approach are still lacking. To explore an immune signature predictive for response, we performed liquid biopsy immunoprofiling in 18 cancer patients undergoing PD-1 inhibition before and shortly after initiation of treatment by multicolor flow cytometry and nextgeneration T-and B-cell immunosequencing (TCRß/IGH). Findings were correlated with clinical outcomes. We found almost complete saturation of surface PD-1 on all T-cell subsets after the first dose of the antibody. Both T-and B-cell compartments quantitatively expanded during treatment. These expansions were mainly driven by an increase in the activated T-cell compartments, as well as of na€ ıve B-and plasma cells. Deep immunosequencing revealed a clear diversification pattern of the clonal T-cell space indicative of antigenic selection in 47% of patients, while the remaining patients showed stable repertoires. 43% of the patients with a diversification pattern showed disease control in response to the PD-1 inhibitor. No disease stabilizations were observed without clonal T-cell space diversification. Our data show for the first time a clear impact of PD-1 targeting not only on circulating T-cells, but also on B-lineage cells, shedding light on the complexity of the anti-tumor immune response. Liquid biopsy T-cell next-generation immunosequencing should be prospectively evaluated as part of a composite response prediction biomarker panel in the context of clinical studies.

Colorectal cancer (CRC) is one of the major causes of cancer-related death and reliable blood-based prognostic biomarkers are urgently needed. The enumeration and molecular characterization of circulating tumor cells (CTCs) has gained increasing interest in clinical practice. CTC detection by CellSearch® has already been correlated to an unfavorable outcome in metastatic CRC. However, the CTC detection rate in mCRC disease is low compared to other tumor entities. Thus, the use of alternative (or supplementary) assays might help to itemize the prognostic use of CTCs as blood-based biomarkers. In this study, blood samples from 47 mCRC patients were screened for CTCs using the FDA-cleared CellSearch® technology and / or the AdnaTest®. 38 samples could be processed in parallel. We demonstrate that a combined analysis of CellSearch® and the AdnaTest® leads to an improved detection of CTCs in our mCRC patient cohort (positivity rate CellSearch® 33%, AdnaTest® 30%, combined 50%). While CTCs detected with the CellSearch® system were significantly associated with progression-free survival (p = 0.046), a significant correlation regarding overall survival could be only seen when both assays were combined (p = 0.013). These findings could help to establish improved tools to detect CTCs as on-treatment biomarkers for clinical routine in future studies.

BackgroundPatients undergoing chemotherapy are highly burdened by side effects. These may be caused by the pharmacodynamics of the drug or be driven by psychological factors such as negative expectations or pre-conditioning, which reflect nocebo effects. As such, negative pre-treatment expectations or prior experiences might exacerbate the burden of chemotherapy side effects. Educating patients about this nocebo effect has been put forward as a potential strategy to optimize patients’ pre-treatment expectations. In this study, we evaluate whether a briefing about the nocebo effect is efficacious in reducing side effects.MethodsIn this exploratory study, a total number of n = 100 outpatients with newly diagnosed gastrointestinal cancers are randomized 1:1 to an information session about the nocebo effect (nocebo-education) or an attention control group (ACG) with matching interaction time. Assessments take place before the intervention (T1 pre), post-intervention (T1 post), and 10 days (T2) and 12 weeks (T3) after the initial chemotherapy. The primary outcomes are the patient-rated number and intensity of side effects at 10-days and at 12-weeks follow-up. Secondary outcomes include coping with side effects, tendency to misattribute symptoms, compliance intention, attitude towards the chemotherapy, co-medication to treat side effects and the clinician-rated severity of toxicity. Further analyses are conducted to investigate whether a potential beneficial effect is mediated by a change of expectations before and after the intervention.DiscussionInforming patients about the nocebo effect might be an innovative and feasible intervention to reduce the burden of side effects and strengthen patients’ perceived control over adverse symptoms.Trial registrationThe trial is registered at the German Clinical Trials Register (ID: DRKS00009501; retrospectively registered on March 27, 2018). The first patient was enrolled on September 29, 2015.

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BackgroundMultimodality treatment improves the chance of survival but increases the risk for long-term side effects in young cancer survivors, so-called” Adolescents and Young Adults“(AYAs). Compared to the general population AYAs have a 5 to 15-fold increased risk of cardiovascular morbidity. Thus, improving modifiable lifestyle risk factors is of particular importance.MethodsThe INAYA trial included AYAs between 18 and 39 years receiving an intensified individual nutrition counseling at four time points in a 3-month period based on a 3-day dietary record. At week 0 and 12 AYAs got a face-to-face counseling, at week 2 and 6 by telephone. Primary endpoint was change in nutritional behavior measured by Healthy Eating Index - European Prospective Investigation into Cancer and Nutrition (HEI-EPIC).ResultsTwenty-three AYAs (11 female, 12 male, median age 20 years (range 19–23 years), median BMI: 21.4 kg/m2 (range: 19.7–23.9 kg/m2) after completion of cancer treatment for sarcoma (n = 2), carcinoma (n = 2), blastoma (n = 1), hodgkin lymphoma (n = 12), or leukemia (n = 6) were included (median time between diagnosis and study inclusion was 44 month).The primary endpoint was met, with an improvement of 20 points in HEI-EPIC score in 52.2 % (n = 12) of AYAs. At baseline, median HEI-EPIC score was 47.0 points (range from 40.0 to 55.0 points) and a good, moderate and bad nutritional intake was seen in 4.3, 73.9 and 21.7 % of AYAs. At week 12, median HEI-EPIC improved significantly to 65.0 points (range from 55.0 to 76.0 points) (p ≤ 0.001) and a good, moderate and bad nutritional intake was seen in 47.8, 52.2 and 0 % of AYAs. No change was seen in quality of life, waist-hip ratio and blood pressure.ConclusionIntensified nutrition counseling is feasible and seem to improve nutritional behavior of AYAs. Further studies will be required to demonstrate long-term sustainability and confirm the results in a randomized design in larger cohorts.Trial registrationClinical trial identifier DRKS00009883 on DRKSElectronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2896-7) contains supplementary material, which is available to authorized users.