Cryoablation: physical and molecular basis with putative immunological consequences

et al. 2020

Breast Cancer�(Auckl)

Introduction: Breast cancer is the most prominent form of cancer and the second leading cause of death in women behind lung cancer. The primary modes of treatment today include surgical excision (lumpectomy, mastectomy), radiation, chemoablation, anti-HER2/neu therapy, and/or hormone therapy. The severe side effects associated with these therapies suggest a minimally invasive therapy with fewer quality of life issues would be advantageous for treatment of this pervasive disease. Cryoablation has been used in the treatment of other cancers, including prostate, skin, and cervical, for decades and has been shown to be a successful minimally invasive therapeutic option. To this end, the use of cryotherapy for the treatment of breast cancer has increased over the last several years. Although successful, one of the challenges in cryoablation is management of cancer destruction in the periphery of the ice ball as the tissue within this outer margin may not experience ablative temperatures. In breast cancer, this is of concern due to the lobular nature of the tumors. As such, in this study, we investigated the level of cell death at various temperatures associated with the margin of a cryogenic lesion as well as the impact of repetitive freezing and thawing methods on overall efficacy. Methods: Human breast cancer cells, MCF-7, were exposed to temperatures of −5°C, −10°C, −15°C, −20°C, or −25°C for 5-minute freeze intervals in a single or repeat freeze-thaw cycle. Samples were thawed with either passive or active warming for 5 or 10 minutes. Samples were assessed at 1, 2, and 3 days post-freeze to assess cell survival and recovery. In addition, the modes of cell death associated with freezing were assessed over the initial 24-hour post-thaw recovery period. Results: Exposure of MCF-7 cells to −5°C and −10°C resulted in minimal cell death regardless of the freeze/thaw conditions. Freezing to a temperature of −25°C resulted in complete cell death 1 day post-thaw with no cell recovery in all freeze/thaw scenarios evaluated. Exposure to a single freeze event resulted in a gradual increase in cell death at −15°C and −20°C. Application of a repeat freeze-thaw cycle (dual 5-minute freeze) resulted in an increase in cell death with complete destruction at −20°C and near complete death at −15°C (day 1 survival: single −15°C freeze/thaw = 20%; repeated −15°C freeze/thaw = 4%). Analysis of thaw interval time (5 vs 10 minute) demonstrated that the shorter 5-minute thaw interval between freezes resulted in increased cell destruction. Furthermore, investigation of thaw rate (active vs passive thawing) demonstrated that active thawing resulted in increased cell survival thereby less effective ablation compared with passive thawing (eg, −15°C 5/10/5 procedure survival, passive thaw: 4% vs active thaw: 29%). Conclusions: In summary, these in vitro findings suggest that freezing to temperatures of 25°C results in a high degree of breast cancer cell destruction. Furthermore, the data demonstrate that the application of a repeat freeze procedure with a passive 5-minute or 10-minute thaw interval between freeze cycles increases the minimal lethal temperature to the −15°C to −20°C range. The data also demonstrate that the use of an active thawing procedure between freezes reduces ablation efficacy at temperatures associated with the iceball periphery. These findings may be important to improving future clinical applications of cryoablation for the treatment of breast cancer.

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Breast Cancer Cryoablation: Assessment of the Impact of Fundamental Procedural Variables in an In Vitro Human Breast Cancer Model

Snyder

Buskirk

et al. 2020

Breast Cancer�(Auckl)

“…[48][49][50][51][52] More recent studies have focused on the combination of immunotherapy and cryoablation to improve cancer destruction, both localized and metastatic disease. 44,[53][54][55] Regardless of the agent utilized, the goal of these efforts is to "make ice lethal at 0°C" while eliciting minimal side effects.…”

Section: Increasing Tissue Destructionmentioning

confidence: 99%

Cryoablation of Prostate- Improving Efficacy and Safety

Polascik

Buskirk

et al. 2020

MRAJ

Cryoablation has been shown to be an effective therapy for all stages of prostate cancer. Though judged efficacious, complications of treatment and persistent disease, although minimal, show the need for improvement. To this end, research has focused on new technology design for cryosurgical apparatus and imaging techniques. Adjunctive therapy, focusing on increasing cell death by apoptosis, also plays a role in this new direction with the intent of increasing cell death in the frozen tissue. Additionally, incorporating methods of protecting adjacent structures, including the urethra, bladder neck sphincter, urogenital diaphragm, neurovascular bundles, and rectum, are critical to achieving a successful outcome and continue to evolve. Several strategies to protect these structures are now commonplace as part of a cryosurgical procedure. These strategies include real-time temperature monitoring, visualization of ice growth during freezing, active heating and even the injection of protective media have emerged as methods to protect these structures. Another more recent procedural application is partial gland ablation or image-targeted focal therapy, developed to maintain cancer control yet minimize the risk of collateral damage to the various structures. Each of these methods has been shown in vitro, in vivo, and clinically to be beneficial. This article describes the directions that cryoablation has taken in an effort to improve procedural efficacy while reducing/eliminating associated co-morbidities.

“…Importantly, cryolesions do not "grow" post treatment whereas heat-based lesions will increase in size (depth) for several days, clinically resulting in a higher risk of complications [11][12][13][14]. Other benefits include depth of penetration, ability to use in combination with other treatments (adjunctive role), likely improved hemostasis and the ability to target non-resectable tumors [15][16][17][18]. Through percutaneous needles or catheter-based approaches, the delivery of cryoablative doses to tissues not traditionally targeted by the therapy have expanded [19][20][21][22][23][24][25][26][27][28][29].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of a Novel Cystoscopic Compatible Cryocatheter for the Treatment of Bladder Cancer

Robilotto

Santucci

et al. 2020

BLC

Self Cite

BACKGROUND: As the acceptance of cryoablative therapies for the treatment of non-metastatic cancers continues to grow, avenues for novel cryosurgical technologies and approaches have opened. Within the field of genitourinary tumors, cryosurgical treatments of bladder cancers remain largely investigational. Current modalities employ percutaneous needles or transurethral cryoballoons or sprays, and while results have been promising, each technology is limited to specific types and stages of cancers. OBJECTIVE: This study evaluated a new, self-contained transurethral cryocatheter, FrostBite-BC, for its potential to treat bladder cancer. METHODS: Thermal characteristics and ablative capacity were assessed using calorimetry, isothermal analyses, in vitro 3-dimensional tissue engineered models (TEMs), and a pilot in vivo porcine study. RESULTS: Isotherm assessment revealed surface temperatures below – 20°C within 9 sec. In vitro TEMs studies demonstrated attainment of ≤– 20°C at 6.1 mm and 8.2 mm in diameter following single and double 2 min freezes, respectively. Fluorescent imaging 24 hr post-thaw revealed uniform, ablative volumes of 326.2 mm3 and 397.9 mm3 following a single or double 2 min freeze. In vivo results demonstrated the consistent generation of ablative areas. Lesion depth was found to correlate with freeze time wherein 15 sec freezes resulted in ablation confined to the sub-mucosa and ≥30 sec full thickness ablation of the bladder wall. CONCLUSIONS: These studies demonstrate the potential of the FrostBite-BC cryocatheter as a treatment option for bladder cancer. Although preliminary, the outcomes of these studies were encouraging, and support the continued investigation into the potential of the FrostBite-BC cryocatheter as a next generation, minimally invasive cryoablative technology.