Poor patient outcome correlates with active engulfment of cytokeratin positive CTCs within cancer-associated monocyte population in lung cancer.

High rates of mortality in non-small cell lung cancer lung cancer is due to inherent and acquired resistance to systemic therapies and subsequent metastatic burden. Metastasis is supported by suppression of the immune system at secondary organs and within the circulation. Modulation of the immune system is now being exploited as a therapeutic target with immune checkpoint inhibitors. The tracking of therapeutic efficacy in a real-time can be achieved with liquid biopsy, and evaluation of circulating tumour cells and the associated immune cells. A stable liquid biopsy biomarker for non-small cell lung cancer lung cancer has yet to be approved for clinical use. We performed a cross-sectional single-site study, and collected liquid biopsies from patients diagnosed with early, locally advanced, or metastatic lung cancer, undergoing surgery, or systemic therapy (chemotherapy/checkpoint inhibitors). Evaluation of overall circulating tumour cell counts, or cluster counts did not correlate with patient outcome. Interestingly, the numbers of Pan cytokeratin positive circulating tumour cells engulfed by tumour associated monocytes correlated strongly with patient outcome independent of circulating tumour cell counts and the use of checkpoint inhibitors. We suggest that Pan cytokeratin staining within monocytes is an important indicator of tumour-associated inflammation post-therapy and an effective biomarker with strong prognostic capability for patient outcome.

A pilot study for presence of circulating tumour cells in adenoid cystic carcinoma.

Adenoid cystic carcinoma (ACC) is a rare salivary gland neoplasm with a poor long-term prognosis due to multiple recurrences and distant metastatic spread. Circulating tumour cells (CTCs) are tumour cells shed from a primary, recurrent, or metastatic cancer that are detectable in the blood or lymphatics. There is no literature to date confirming the presence of CTCs in ACC. The aim of this study was to determine whether CTCs are detectable in ACC. Blood samples were collected from eight patients with histologically confirmed ACC. The TNM stage of the tumour was recorded, as well as any prior treatment. CTCs were isolated by spiral microfluidics and detected by immunofluorescence staining. Three of the eight patients recruited (32.5%) had staining consistent with the presence of CTCs. Of these three patients with detectable CTCs, one had confirmed pulmonary metastasis, one had suspected pulmonary metastasis and was awaiting confirmation, and one had local recurrence confirmed on re-resection. One patient with known isolated pulmonary metastasis had previously undergone a lung metastasectomy and did not have CTCs detected. CTCs are detectable in ACC. In this small patient sample, CTCs were found to be present in those patients with recurrent local disease and known distant metastatic disease. CTCs in ACC should be investigated further for their potential use as an adjunct in staging, prognosis, and the detection of recurrence.

Melanoma circulating tumor cells: Benefits and challenges required for clinical application.

The implementation of novel therapeutic interventions has improved the survival rates of melanoma patients with metastatic disease. Nonetheless, only 33% of treated cases exhibit long term responses. Circulating tumor cell (CTC) measurements are currently of clinical value in breast, prostate and colorectal cancers. However, the clinical utility of melanoma CTCs (MelCTCs) is still unclear due to challenges that appear intrinsic to MelCTCs (i.e. rarity, heterogeneity) and a lack of standardization in their isolation, across research laboratories. Here, we review the latest developments, pinpoint the challenges in MelCTC isolation and address their potential role in melanoma management.