Significance of circulating tumor cells in osteosarcoma patients treated by neoadjuvant chemotherapy and surgery

Wu, Zhenjie; Tan, Jiachang; Xiong, Qin; Liu, Bin; Yuan, Zhenchao

doi:10.2147/cmar.s176515

Cited by 26 publications

(26 citation statements)

References 21 publications

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“…Limited studies of OSA CTC in humans also report a higher number than typically noted for carcinomas, but not nearly as high as those in our study (30,31,44). OSA is a highly aggressive neoplasm in dogs, and circulating OSA cells may at times be observed even on routine blood smear review (data not shown); therefore, frequent CTCs may be a biological feature of the tumor.…”

Section: Discussioncontrasting

confidence: 52%

“…OSA is a highly aggressive neoplasm in dogs, and circulating OSA cells may at times be observed even on routine blood smear review (data not shown); therefore, frequent CTCs may be a biological feature of the tumor. Limited studies of OSA CTC in humans also report a higher number than typically noted for carcinomas, but not nearly as high as those in our study (30,31,44). Strengths of our study are that blood samples from dogs were analyzed multiple times, including immediately before death, which provided a dynamic picture of CTC frequency.…”

Section: Discussionmentioning

confidence: 42%

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Flow Cytometric Detection of Circulating Osteosarcoma Cells in Dogs

et al. 2019

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Osteosarcoma (OSA) is a malignant tumor of middle-aged dogs and adolescent humans. The clinical outcome of OSA has not improved over more than three decades, and dogs typically succumb to metastatic disease within 6 months despite tumor resection through limb amputation and adjuvant chemotherapy. Therefore, undetectable tumor cells with potential to form metastases are present at diagnosis. An assay to identify canine immortalized and primary OSA cells through flow cytometric detection of intracellular collagen 1 (Col I) and osteocalcin was optimized, and applied to blood samples from tumorbearing dogs for detection of circulating tumor cells (CTCs). Spiking variable number of OSA cells into normal dog blood recovered 50-60% of Col I positive cells with high forward and variable side light scatter. An algorithm to exclude nonviable, doublet, and autofluorescent cells was applied to sequential blood samples from three dogs obtained prior to and after limb amputation, and at approximately, triweekly intervals over 121, 142, and 183 days of chemotherapy, respectively. Dogs had >100 CTC/10 6 leukocytes prior to amputation, variably frequent CTC during chemotherapy, and an increase up to 4,000 CTC/10 6 leukocytes within 4 weeks before overt metastases or death. Sorted CTCs were morphologically similar to direct tumor aspirates and positive for Col I. Although preliminary, findings suggest that CTCs are frequent in canine OSA, more numerous than carcinoma CTC in humans, and that an increase in CTC frequency may herald clinical deterioration. This assay may enable enumeration and isolation of OSA CTC for prognostic and functional studies, respectively. OSTEOSARCOMA (OSA) is a primary bone cancer that is common in middle-aged to older, large breed dogs, and less common in humans, where children and young adults are most often affected. Therapy consisting of limb amputation or limbsparing tumor resection followed by chemotherapy (typically platinum or doxorubicin-based) is the gold standard, but the clinical outcome of OSA in dogs and humans remains poor (1-3). Dogs with OSA of the appendicular skeleton treated with amputation and chemotherapy had median survival times (STs) of 235-540 days (4), while in humans 5-year survival has been stagnant at about 60% (5). Although the median ST is relatively homogeneous, the range of ST in dogs with OSA treated identically varies from 2 to >30 months, illustrating that there is extensive heterogeneity in tumor biology and/or host response (6-8). Metastatic disease is the usual cause of spontaneous death or euthanasia, but fewer than 10% of dogs have radiographic evidence of metastasis at the time of diagnosis (2).Computed tomography also lacks sensitivity for identifying metastases, and histologic grading schemes for canine OSA poorly predict biological behavior (9-11).

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Section: Discussioncontrasting

confidence: 52%

Section: Discussionmentioning

confidence: 42%

Flow Cytometric Detection of Circulating Osteosarcoma Cells in Dogs

et al. 2019

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“…However, only CTCs expressing epithelial cell adhesion molecule (EpCAM) will be identified with the CellSearch system . Compared with the CellSearch platform, which uses anti‐EpCAM‐coated magnetic beads to capture CTCs, one study found that patients with an increased percentage of mesenchymal CTCs (M‐CTCs) after treatment had a worse prognosis based on CanPatrol technology . The CanPatrol technique could identify CTCs expressing both epithelial‐ and mesenchymal type‐related antigens.…”

Section: Discussionmentioning

confidence: 99%

“…39,43 Compared with the CellSearch platform, which uses anti-EpCAM-coated magnetic beads to capture CTCs, one study found that patients with an increased percentage of mesenchymal CTCs (M-CTCs) after treatment had a worse prognosis based on CanPatrol technology. 44 The CanPatrol technique could identify CTCs expressing both epithelialand mesenchymal type-related antigens. Moreover, as a result of 99.98% of leukocytes being depleted and a low number of leukocytes remaining on the membrane, it is easier to observe CTCs under a microscope with the CanPatrol technique.…”

Section: Discussionmentioning

confidence: 99%

Prospective study of the relevance of circulating tumor cell status and neoadjuvant chemotherapy effectiveness in early breast cancer

Fang

Zhang

et al. 2020

Cancer Medicine

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Although unequivocal evidence has shown the prognostic relevance of circulating tumor cells (CTCs) in patients with metastatic breast cancer (MBC), less evidence is available for its significance in neoadjuvant chemotherapy (NCT) in early breast cancer (BC). Here we conducted an analysis of individual data from 86 patients confirmed as invasive BC by core‐needle biopsy in Zhejiang Provincial People's Hospital between June 2013 and January 2017. The CTCs were assessed at the time after diagnosis and before surgery with the CanPatrol technique. The median follow‐up duration was 46.3 months. CTCs were detected in 37.2% of all patients (29/78) at baseline, and the presence of CTCs was associated with tumor size, tumor stage, and molecular classification. After NCT, the CTC‐positive patients were dropped from 29 to 8, and the EC‐T (epirubicin/cyclophosphamide followed by docetaxel) and TEC (docetaxel/epirubicin/cyclophosphamide) strategies reduce CTC‐positive patients from 16 to 3 and 13 to 5, respectively. The CTC‐negative conversion rates were similar in ER/PR+ HER2+ (5/7, 71.4%), ER/PR− HER2+ (8/11, 72.7%), and TNBC (7/10, 70%) during NCT. In addition, we explored the association between CTC‐negative conversion and objective response rate (partial response and complete response, ORR) and pathological complete response rate (pCR), and our results indicate that ORR was higher in patients with positive CTCs and converted to negative after NCT (ORR, P = .013; pCR, P = .0608). Our study preliminarily highlights the relevance of CTC status and NCT effectiveness in early BC using the CanPatrol system.

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“…Osteosarcoma (OS) is a common cancer of the musculoskeletal system in teens and is a leading cause of cancer death and disability worldwide [1]. The most involved sites are the distal femur, the proximal humerus, the proximal tibia, and the metaphysis [2]. The age of peak incidence rate ranges from 14 to 26 years old, especially 14 to 19 years old, and this constitutes a separate specific subgroup who suffer osteosarcoma [3].…”

Section: Introductionmentioning

confidence: 99%

The Value of Intravoxel Incoherent Motion (IVIM) Magnetic Resonance Imaging in the Evaluation of the Osteosarcoma Response to Preoperative Neoadjuvant Chemotherapy in Teens

Zuo

2019

Concepts in Magnetic Resonance Part A

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Purpose. To investigate the value of intravoxel incoherent motion (IVIM) magnetic resonance imaging in the evaluation of the osteosarcoma (OS) response to preoperative neoadjuvant chemotherapy (NAC) in teens. Methods. Eighteen consecutive osteosarcoma patients (12 males and 6 females) diagnosed by histopathology were enrolled. All enrolled patients received NAC and underwent MRI examinations before and after 2 cycles of NAC. The volume (V), apparent diffusion coefficient (ADC), (slow) diffusion coefficient (D), pseudo-perfusion (fast) diffusion coefficient (D⁎or D star), and perfusion fractions (f) of the OS before and after NAC were measured and analysed. The sensitivity and the specificity of the ADC, D, D⁎ and f values and the correlation between changes in volume (ΔV) and the IVIM-derived parameters (ΔADC, ΔD, ΔD⁎ and Δf) were also calculated and analysed. Paired Student’s t-tests, receiver operating characteristic (ROC) curves, and Spearman correlation analyses were used. Results. The mean volume of the OS after NAC decreased significantly (61.55±9.3 cm3 vs 40.26±4.1 cm3) (P<0.05). After NAC, the ADC (1.21±0.09 × 10-3 mm2/s vs 1.73±0.11 × 10-3 mm2/s) and D (1.14±0.09 × 10-3 mm2/s vs 1.63±0.1 × 10-3 mm2/s) values increased and f (28.58±1.37% vs 20.93±1.16%) values decreased significantly (P<0.05), while D⁎ (9.17±0.98 × 10-3 mm2/s vs 8.94±0.13 × 10-3 mm2/s) values changed slightly (P>0.05). The AUC values of ADC (0.938) and D (0.943) were higher than those of D⁎ (0.574) and f (0.765). The sensitivity and specificity of ADC (0.778, 1) and D (0.944, 0.833) values were superior to those of D⁎ (0.278, 0.722) and f (0.5, 0.944) values. No significant correlations were found between the ΔV and ΔADC, ΔD, ΔD⁎ and Δf values (P>0.05). Conclusion. IVIM-derived parameters ADC and D have the potential to be imaging biomarkers for evaluation of the therapeutic response to NAC in OS patients.

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Significance of circulating tumor cells in osteosarcoma patients treated by neoadjuvant chemotherapy and surgery

Cited by 26 publications

References 21 publications

Flow Cytometric Detection of Circulating Osteosarcoma Cells in Dogs

Flow Cytometric Detection of Circulating Osteosarcoma Cells in Dogs

Prospective study of the relevance of circulating tumor cell status and neoadjuvant chemotherapy effectiveness in early breast cancer

The Value of Intravoxel Incoherent Motion (IVIM) Magnetic Resonance Imaging in the Evaluation of the Osteosarcoma Response to Preoperative Neoadjuvant Chemotherapy in Teens

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