Minimally-invasive breast interventions : methods for high yield, low risk, precision biopsy and curative thermal ablation

Abstract

Advances in medical imaging and the introduction of population-based screening programs have increased the detection rate and overall proportion of small breast tumors. In addition, progress in technology and medical science, in combination with efforts to minimize morbidity, have resulted in the emergence of minimally invasive image-guided interventional procedures for both diagnosis and treatment of breast cancer. The aim of this thesis was to develop and validate new technologies for minimally-invasive diagnosis and treatment of breast cancer. Specifically, to develop and validate a new biopsy system incorporating novel mechanisms for needle insertion and tissue acquisition designed for accurate lesion targeting and high yield tissue sampling; to clinically validate a biopsy enhancement technology using radiofrequency (RF) pulses to counteract dissemination of tumor cells; and to improve and validate radiofrequency ablation (RFA) for the treatment of small carcinoma and demonstrate feasibility in non-operable elderly patients.

During the course of this work a new biopsy device has been developed which incorporates a pneumatic insertion mechanism combined with a novel needle design. Paper I presented the device, compared sampling performance to a standard core needle biopsy (CNB) device in three representative bench models, measured needle dynamics on a specially designed needle trajectory test and evaluated ex vivo sample quality. Mean weight of samples were 3.5, 4.6, and 4.3 times higher (p <0.01) than standard CNB device in turkey breast, calf thymus and swine pancreas. The method of tissue acquisition had no negative impact on the histopathologic quality of samples obtained from resected specimens. Maximum measured needle velocity was 21.2 ±2.5 m/s on a stroke length of 2.5 mm. Paper II investigated whether a technology incorporating the application of RF pulses to the biopsy needle could counteract dissemination of tumor cells. In this proof-of-principle setting the technology was adapted to fine needle aspiration (FNA) and prospectively used in 31 patients. Eighty-eight patients underwent routine FNA. Blood emerging from the skin orifice was analyzed for the presence of tumor cells. Viable tumor cells were found in 74% (65/88) of cases for routine FNA and in 0% (0/31) of cases (p <0.001) when RF pulses where applied. It was observed that application of RF pulses had a hemostatic effect, did not degrade the cytological sample inside the needle and caused no additional pain compared with standard FNA.

In Papers III, IV & V, the technology, method and protocol for RFA in breast cancer were successively developed and evaluated in a total of 55 patients. Specifically, in Paper III the feasibility of a newly developed RF device for ablation of unifocal breast carcinoma <16 mm immediately prior to partial mastectomy was assessed. In 84% (26/31) of cases complete ablation was achieved as assessed by Hematoxylin and Eosin (H&E) staining. Non-complete ablation was associated with incorrect electrode positioning within the lesion and underestimation of lesion extent due to inaccurate preoperative imaging. In Paper IV, tumors ≤20 mm were included and the feasibility under local anesthesia three weeks prior to planned resection using improved technology and protocol was assessed. Magnetic resonance imaging (MRI) was utilized for patient selection. Exclusion criteria included multifocality, diffuse growth patterns, >25% intraductal components and lobular histology. Magnetic resonance imaging, H&E staining and cytokeratine 8 (CK8) immunostaining were used to determine complete ablation. A pneumatic–mechanical insertion mechanism was developed to improve electrode insertion and positioning. Pain was assessed using the Visual Analogue Scale (VAS). In 100% (18/18) of cases MRI showed no residual tumor growth and devitalization of the entire tumor was shown by at least one histologic method. Pain was reported to be a median of 2 and 2.5 for injection of anesthetics and during ablation, respectively, and the difference was not significant (p =0.512). In Paper V the feasibility of RFA as an alternative to surgical resection in elderly breast cancer patients with severe comorbidities that were unfit for or refused surgery was assessed. Six patients aged ≥85 years were included. In all cases, complete ablation was confirmed using MRI and contrast enhanced ultrasound (CEUS) at 1 month as well as staining assays for H&E and CK8 in tissue samples at 6 months. The procedure was well tolerated with mild to moderate pain during the ablation procedure. Follow-up was a median (range) of 54 months (11 to 94 months). Three patients died of non-cancer related causes. Three patients remained alive at 74, 86 and 94 months of which one experienced a loco-regional recurrence at 59 months.

In conclusion, this thesis demonstrates that the newly developed biopsy system enables for a novel method of precision needle insertion and achieves high yield tissue sampling. Furthermore, this thesis demonstrates that the presented biopsy enhancement technology can prevent dissemination of tumor cells. Finally, it demonstrates that RF ablation of small breast carcinoma has a high rate of complete ablation, can be performed under local anesthesia with mild to moderate pain, and is feasible as an individualized treatment option in elderly patients with severe co-morbidity who are refusing, or are unfit for surgery.