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Treatment of advanced solid tumours with NSAIDs: Correlation of quantitative monitoring of circulating tumour cells and positron emission tomography-computed tomography imaging

View Article: PubMed Central - PubMed

ABSTRACT

The detection and characterisation of tumour-derived circulating epithelial tumor cells (CETCs) or circulating tumor cells (CTCs) have been a main focus of basic oncological research over previous years. Numerous studies in the past decade have shown that CTCs are a promising tool for the estimation of the risk for metastatic relapse. The present observational study describes treatment results using tumour imaging and the quantification of CTCs. A group of 14 patients with advanced carcinomas was followed during their anticancer treatments. CTC numbers were serially detected and treatment success was estimated by positron emission tomography-computed tomography. A connection was found between tumour remission and a decreasing CTC count in 83%, a connection between stable disease and stable CTC numbers in 78% and a connection between progressive disease (PD) and an increase in CTC count in 50% of cases. In the patients with PD, an incomplete response was observed affecting the CTCs, but not the solid region of the tumour. As a result of this study, it may be concluded that patients with solid tumours benefit from serial quantification of CTCs in addition to imaging, as this combination of techniques provides a more sensitive result than imaging alone.

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Treatment courses of cancer patients (A-C) Serial CTC assessment: Three patients are shown for whom diagnoses and specific therapies were as follows: (A) Endocervical carcinoma, two treatment periods of diflunisal (yellow bar) followed by tamoxifen/bevacizumab treatment (violet/blue bar); (B) ovarian carcinoma, diflunisal treatment (yellow bar) followed by paclitaxel/bevacizumab and paclitaxel treatments (red and blue bars), doxorubicin/bevacizumab (striped and blue bars) and cyclophosphamide/bevacizumab (green/blue bars); (C) mammary carcinoma, two treatment periods of diflunisal (yellow bar) followed by low-dose capecitabine/trofosfamide/bevacizumab treatment (striped orange/pale blue/white bar). Orange arrows indicate time points for chemosensitivity testing. Blue triangles indicate time points for positron emission tomography-computed tomography. CTC numbers refer to 1 ml blood. CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; CTC, circulating tumor cell.
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f1-ol-0-0-4878: Treatment courses of cancer patients (A-C) Serial CTC assessment: Three patients are shown for whom diagnoses and specific therapies were as follows: (A) Endocervical carcinoma, two treatment periods of diflunisal (yellow bar) followed by tamoxifen/bevacizumab treatment (violet/blue bar); (B) ovarian carcinoma, diflunisal treatment (yellow bar) followed by paclitaxel/bevacizumab and paclitaxel treatments (red and blue bars), doxorubicin/bevacizumab (striped and blue bars) and cyclophosphamide/bevacizumab (green/blue bars); (C) mammary carcinoma, two treatment periods of diflunisal (yellow bar) followed by low-dose capecitabine/trofosfamide/bevacizumab treatment (striped orange/pale blue/white bar). Orange arrows indicate time points for chemosensitivity testing. Blue triangles indicate time points for positron emission tomography-computed tomography. CTC numbers refer to 1 ml blood. CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; CTC, circulating tumor cell.

Mentions: An increase in cell numbers is assumed to correspond to high tumour activity and poor prognosis (13). The results from the present study showed that the behaviour of CTC numbers correlates well with the imaging response. The positive imaging response (CR or PR) correlated with a CTC reduction in 5/6 (83%; P=0.030) of cases. The assessment of a SD correlated with a stable CTC course in 7/9 cases (78%; P<0.001). The assessment of a PD revealed no correlation with an increase in cell numbers in 6/12 (50%; P=0.368) of cases (Table IV). The χ2 test confirmed that PET-CT outcome and CTC course were significantly correlated (P=0.0018). Fig. 1 shows three examples of individual treatment courses. CTC quantity was measured during the treatment periods and for follow-up. A patient who was suffering from an endocervical carcinoma started with stable CTC numbers during the initial diflunisal treatment (Fig. 1A). The following decrease from 600 to 0 cells was accompanied by a CR, and the following rise was accompanied by PD. Thereafter, a tamoxifen/bevacizumab treatment resulted in a PR, which was accompanied by stable CTC numbers (Fig. 1A). The patient in Fig. 1B exhibited rising CTC numbers during the paclitaxel/bevacizumab treatment, but then falling tumour cell numbers indicated successful treatment. Rising cell numbers during paclitaxel treatment have been previously observed and are assumed to originate from enhanced cell dissemination from the primary tumour and most probably also from metastases (19). The treatment success was also reflected by a PR. After the chemotherapy, cell numbers were rising and could be again reduced by paclitaxel therapy. However, 3 months later, PD was observed despite previously falling numbers. Whether a repeated increase in cell numbers, as had been observed prior to the previous progression, had occurred could not be evaluated, since the next analysis was performed only after an additional treatment. Thereafter a stable CTC course resulting from treatments with doxorubicin/bevacizumab and cyclophosphamide/bevacizumab treatment was reflected by findings of SD in PET-CT. Furthermore, the CTC course of a breast cancer patient (Fig. 1C) showed a decrease in the number of CTCs after a 4-week diflunisal treatment. Subsequent rising CTC numbers were accompanied by PD. Another diflunisal treatment (for 4 weeks) and the following low-dose chemotherapy resulted in a decrease in CTC numbers, while the disease continued to progress, as indicated in Fig. 1C. Again, it was assumed that this was an incomplete response characterized by a positive response on the CTC level, but PD observed by the imaging technique.


Treatment of advanced solid tumours with NSAIDs: Correlation of quantitative monitoring of circulating tumour cells and positron emission tomography-computed tomography imaging
Treatment courses of cancer patients (A-C) Serial CTC assessment: Three patients are shown for whom diagnoses and specific therapies were as follows: (A) Endocervical carcinoma, two treatment periods of diflunisal (yellow bar) followed by tamoxifen/bevacizumab treatment (violet/blue bar); (B) ovarian carcinoma, diflunisal treatment (yellow bar) followed by paclitaxel/bevacizumab and paclitaxel treatments (red and blue bars), doxorubicin/bevacizumab (striped and blue bars) and cyclophosphamide/bevacizumab (green/blue bars); (C) mammary carcinoma, two treatment periods of diflunisal (yellow bar) followed by low-dose capecitabine/trofosfamide/bevacizumab treatment (striped orange/pale blue/white bar). Orange arrows indicate time points for chemosensitivity testing. Blue triangles indicate time points for positron emission tomography-computed tomography. CTC numbers refer to 1 ml blood. CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; CTC, circulating tumor cell.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4997972&req=5

f1-ol-0-0-4878: Treatment courses of cancer patients (A-C) Serial CTC assessment: Three patients are shown for whom diagnoses and specific therapies were as follows: (A) Endocervical carcinoma, two treatment periods of diflunisal (yellow bar) followed by tamoxifen/bevacizumab treatment (violet/blue bar); (B) ovarian carcinoma, diflunisal treatment (yellow bar) followed by paclitaxel/bevacizumab and paclitaxel treatments (red and blue bars), doxorubicin/bevacizumab (striped and blue bars) and cyclophosphamide/bevacizumab (green/blue bars); (C) mammary carcinoma, two treatment periods of diflunisal (yellow bar) followed by low-dose capecitabine/trofosfamide/bevacizumab treatment (striped orange/pale blue/white bar). Orange arrows indicate time points for chemosensitivity testing. Blue triangles indicate time points for positron emission tomography-computed tomography. CTC numbers refer to 1 ml blood. CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; CTC, circulating tumor cell.
Mentions: An increase in cell numbers is assumed to correspond to high tumour activity and poor prognosis (13). The results from the present study showed that the behaviour of CTC numbers correlates well with the imaging response. The positive imaging response (CR or PR) correlated with a CTC reduction in 5/6 (83%; P=0.030) of cases. The assessment of a SD correlated with a stable CTC course in 7/9 cases (78%; P<0.001). The assessment of a PD revealed no correlation with an increase in cell numbers in 6/12 (50%; P=0.368) of cases (Table IV). The χ2 test confirmed that PET-CT outcome and CTC course were significantly correlated (P=0.0018). Fig. 1 shows three examples of individual treatment courses. CTC quantity was measured during the treatment periods and for follow-up. A patient who was suffering from an endocervical carcinoma started with stable CTC numbers during the initial diflunisal treatment (Fig. 1A). The following decrease from 600 to 0 cells was accompanied by a CR, and the following rise was accompanied by PD. Thereafter, a tamoxifen/bevacizumab treatment resulted in a PR, which was accompanied by stable CTC numbers (Fig. 1A). The patient in Fig. 1B exhibited rising CTC numbers during the paclitaxel/bevacizumab treatment, but then falling tumour cell numbers indicated successful treatment. Rising cell numbers during paclitaxel treatment have been previously observed and are assumed to originate from enhanced cell dissemination from the primary tumour and most probably also from metastases (19). The treatment success was also reflected by a PR. After the chemotherapy, cell numbers were rising and could be again reduced by paclitaxel therapy. However, 3 months later, PD was observed despite previously falling numbers. Whether a repeated increase in cell numbers, as had been observed prior to the previous progression, had occurred could not be evaluated, since the next analysis was performed only after an additional treatment. Thereafter a stable CTC course resulting from treatments with doxorubicin/bevacizumab and cyclophosphamide/bevacizumab treatment was reflected by findings of SD in PET-CT. Furthermore, the CTC course of a breast cancer patient (Fig. 1C) showed a decrease in the number of CTCs after a 4-week diflunisal treatment. Subsequent rising CTC numbers were accompanied by PD. Another diflunisal treatment (for 4 weeks) and the following low-dose chemotherapy resulted in a decrease in CTC numbers, while the disease continued to progress, as indicated in Fig. 1C. Again, it was assumed that this was an incomplete response characterized by a positive response on the CTC level, but PD observed by the imaging technique.

View Article: PubMed Central - PubMed

ABSTRACT

The detection and characterisation of tumour-derived circulating epithelial tumor cells (CETCs) or circulating tumor cells (CTCs) have been a main focus of basic oncological research over previous years. Numerous studies in the past decade have shown that CTCs are a promising tool for the estimation of the risk for metastatic relapse. The present observational study describes treatment results using tumour imaging and the quantification of CTCs. A group of 14 patients with advanced carcinomas was followed during their anticancer treatments. CTC numbers were serially detected and treatment success was estimated by positron emission tomography-computed tomography. A connection was found between tumour remission and a decreasing CTC count in 83%, a connection between stable disease and stable CTC numbers in 78% and a connection between progressive disease (PD) and an increase in CTC count in 50% of cases. In the patients with PD, an incomplete response was observed affecting the CTCs, but not the solid region of the tumour. As a result of this study, it may be concluded that patients with solid tumours benefit from serial quantification of CTCs in addition to imaging, as this combination of techniques provides a more sensitive result than imaging alone.

No MeSH data available.


Related in: MedlinePlus