Irreversible electroporation

Last updated
Irreversible electroporation
Other namesNon-thermal irreversible electroporation
Specialty oncology

Irreversible electroporation or IRE is a soft tissue ablation technique using short but strong electrical fields to create permanent and hence lethal nanopores in the cell membrane, to disrupt cellular homeostasis. The resulting cell death results from induced apoptosis or necrosis induced by either membrane disruption or secondary breakdown of the membrane due to transmembrane transfer of electrolytes and adenosine triphosphate. [1] [2] [3] [4] The main use of IRE lies in tumor ablation in regions where precision and conservation of the extracellular matrix, blood flow and nerves are of importance. The first generation of IRE for clinical use, in the form of the NanoKnife System, became commercially available for research purposes in 2009, solely for the surgical ablation of soft tissue tumors. [5] Cancerous tissue ablation via IRE appears to show significant cancer specific immunological responses which are currently being evaluated alone and in combination with cancer immunotherapy. [6] [7] [8] [9]

Contents

History

First observations of IRE effects go back to 1754. Nollet reported the first systematic observations of the appearance of red spots on animal and human skin that was exposed to electric sparks. [10] However, its use for modern medicine began in 1982 with the seminal work of Neumann and colleagues. [11] Pulsed electric fields were used to temporarily permeabilize cell membranes to deliver foreign DNA into cells. In the following decade, the combination of high-voltage pulsed electric fields with the chemotherapeutic drug bleomycin and with DNA yielded novel clinical applications: electrochemotherapy and gene electrotransfer, respectively. [12] [13] [14] [15] [16] The use of irreversible electroporation for therapeutic applications was first suggested by Davalos, Mir, and Rubinsky. [17]

Mechanism

Utilizing ultra short pulsed but very strong electrical fields, micropores and nanopores are induced in the phospholipid bilayers which form the outer cell membranes.[ citation needed ] Two kinds of damage can occur:

  1. Reversible electroporation (RE): Temporary and limited pathways for molecular transport via nanopores are formed, but after the end of the electric pulse, the transport ceases and the cells remain viable. Medical applications are, for example, local introduction of intracellular cytotoxic pharmaceuticals such as bleomycin (electroporation and electrochemotherapy).[ citation needed ]
  2. Irreversible electroporation (IRE): After a certain degree of damage to the cell membranes by electroporation, the leakage of intracellular contents is too severe or the resealing of the cellular membrane is too slow, leaving healthy and/or cancerous cells irreversibly damaged. They die by either apoptosis or via cell-internally induced necrotic pathways, which is unique to this ablation technique.[ citation needed ]

It should be stated that even though the ablation method is generally accepted to be apoptosis, some findings seem to contradict a pure apoptotic cell death, making the exact process by which IRE causes cell death unclear. [18] [4] In any case, all studies agree that the cell death is an induced one with the cells dying over a varying time period of hours to days and does not rely on local extreme heating and melting of tissue via high energy deposition like most ablation technologies (see radiofrequency ablation, microwave ablation, High-intensity focused ultrasound).[ citation needed ]

When an electrical field of more than 0.5 V/nm [19] is applied to the resting trans-membrane potential, it is proposed that water enters the cell during this dielectric breakdown. Hydrophilic pores are formed. [20] [21] A molecular dynamics simulation by Tarek [22] illustrates this proposed pore formation in two steps: [23]

  1. After the application of an electrical field, water molecules line up in single file and penetrate the hydrophobic center of the bilayer lipid membrane.
  2. These water channels continue to grow in length and diameter and expand into water-filled pores, at which point they are stabilized by the lipid head groups that move from the membrane-water interface to the middle of the bilayer.

It is proposed that as the applied electrical field increases, the greater is the perturbation of the phospholipid head groups, which in turn increases the number of water filled pores. [24] This entire process can occur within a few nanoseconds. [22] Average sizes of nanopores are likely cell-type specific. In swine livers, they average around 340-360 nm, as found using SEM. [23]

A secondary described mode of cell death was described to be from a breakdown of the membrane due to transmembrane transfer of electrolytes and adenosine triphosphate. [3] Other effects like heat [25] or electrolysis [26] [27] were also shown to play a role in the currently clinically applied IRE pulse protocols.

Potential advantages and disadvantages

Advantages of IRE

  1. Tissue selectivity - conservation of vital structures within the treatment field. Its capability of preserving vital structures within the IRE-ablated zone. In all IRE ablated liver tissues, critical structures, such as the hepatic arteries, hepatic veins, portal veins and intrahepatic bile ducts were all preserved. As IRE targets the bilipid membranes of cells, structures mainly consisting of proteins like vascular elastic and collagenous structures, as well as peri-cellular matrix proteins are not affected by the currents. Vital and scaffolding structures (like large blood vessels, urethra or intrahepatic bile ducts) are conserved. [28] The electrically insulating myelin layer, surrounding nerve fibers, protects nerve bundles from the IRE effects to a certain degree. Up to what point nerves stay unaffected or can regenerate is not completely understood. [29]
  2. Sharp ablation zone margins- The transition zone between reversible electroporated area and irreversible electroporated area is accepted to be only a few cell layers. Whereas, the transition areas as in radiation or thermal based ablation techniques are non-existent. Further, the absence of the heat sink effect, which is a cause of many problems and treatment failures, is advantageous and increases the predictability of the treatment field. Geometrically, rather complex treatment fields are enabled by the multi-electrode concept. [30]
  3. Absence of thermally induced necrosis - The short pulse lengths relative to the time between the pulses prevents joule heating of the tissue. Hence, by design, no necrotic cell damage is to be expected (except possibly in very close proximity to the needle). Therefore, IRE has none of the typical short and long term side-effects associated with necrosis. [31] [32]
  4. Short treatment time - A typical treatment takes less than 5 minutes. This does not include the possibly complicated electrode placement which might require the use of many electrode and re-position of the electrodes during the procedure.
  5. Real time monitoring - The treatment volume can be to a certain degree be visualized, both during and after the treatment. Possible visualization methods are ultrasound, MRI, and CT. [30]
  6. Immunological response - IRE appears to provoke a stronger immunological response than other ablation methods [8] which is currently being studied for use in conjunction with cancer immunotheraputic approaches. [6]

Disadvantages of IRE

  1. Strong muscle contractions - The strong electric fields created by IRE, due to direct stimulation of the neuromuscular junction, cause strong muscle contractions requiring special anesthesia and total body paralysis. [33]
  2. Incomplete ablation within targeted tumors - The originally threshold for IRE of cells was approximately 600 V/cm with 8 pulses, a pulse duration of 100 μs, and a frequency of 10 Hz. [34] Qin et al. later discovered that even at 1,300 V/cm with 99 pulses, a pulse duration of 100 μs, and 10 Hz, there were still islands of viable tumor cells within ablated regions. [35] This suggests that tumor tissue may respond differently to IRE than healthy parenchyma. The mechanism of cell death following IRE relies on cellular apoptosis, which results from pore formation in the cellular membrane. Tumor cells, known to be resistant to apoptotic pathways, may require higher thresholds of energy to be adequately treated. However, the recurrence rated found in clinical studies suggest a rather low recurrence rate and often superior overall survival when compared with other ablation modalities. [36] [37]
  3. Local environment - The electric fields of IRE are strongly influenced by the conductivity of the local environment. The presence of metal, for example with biliary stents, can result in variances in energy deposition. Various organs, such as the kidneys, are also subject to irregular ablation zones, due to the increased conductivity of urine. [38]

Use in medical practice

A number of electrodes, in the form of long needles, are placed around the target volume. The point of penetration for the electrodes is chosen according to anatomical conditions. Imaging is essential to the placement and can be achieved by ultrasound, magnetic resonance imaging or tomography. The needles are then connected to the IRE-generator, which then proceeds to sequentially build up a potential difference between two electrodes. The geometry of the IRE-treatment field is calculated in real time and can be influenced by the user. Depending on the treatment-field and number of electrodes used, the ablation takes between 1 and 10 minutes. In general muscle relaxants are administered, since even under general anesthetics, strong muscle contractions are induced by excitation of the motor end-plate.[ citation needed ]

Typical parameters (1st generation IRE system):[ citation needed ]

The shortly pulsed, strong electrical fields are induced through thin, sterile, disposable electrodes. The potential differences are calculated and applied by a computer system between these electrodes in accordance to a previously planned treatment field. [39]

One specific device for the IRE procedure is the NanoKnife system manufactured by AngioDynamics, which received FDA 510k clearance on October 24, 2011. [40] The NanoKnife system has also received an Investigational Device Exemption (IDE) from the FDA that allows AngioDynamics to conduct clinical trials using this device. [40] The Nanoknife system transmits a low-energy direct current from a generator to electrode probes placed in the target tissues for the surgical ablation of soft tissue. In 2011, AngioDynamics received an FDA warning letter for promoting the device for indications for which it had not received approval. [41]

In 2013, the UK National Institute for Health and Clinical Excellence issued a guidance that the safety and efficacy of the use of irreversible electroporation of the treatment of various types of cancer has not yet been established. [42]

Newer generations of Electroporation-based ablation systems are being developed specifically to address the shortcomings of the first generation of IRE but, as of June 2020, none of the technologies are available as a medical device. [27] [43] [44]

Clinical data

Potential organ systems, where IRE might have a significant impact due to its properties include the pancreas, liver, prostate and the kidneys, which were the main focus of the studies listed in Table 1-3 (state: June 2020).

None of the potential organ systems, which may be treated for various conditions and tumors, are covered by randomized multicenter trials or long-term follow-ups (state. June 2020).

Liver

Table 1: Irreversible Electroporation Clinical Data in the Liver [36]
Author, YearNo. of Patients / LesionsTumor Type and median sizeApproachMedian follow-up (mo)Primary efficacy [45] (%)Secondary efficacy [45] (%)
Frühling et al. 2023 [46] 149 / 149CRLM (n = 87), HCC (n = 62)NA58Mean Overall Survival : 27.0 months (95% CI 22.2–31.8 months), and 35.0 months (95% CI 13.8–56.2 months),NS
Bhutiani et al.,

2016 [47]

30 / 30HCC (n = 30),

3.0 cm

Open (n = 10),

laparoscopic (n = 20)

697NS
Cannon et al.,

2013 [48]

44 / 48HCC (n = 14),

CRLM (n = 20), Other (n = 10); 2.5 cm

Percutaneous

(n = 28), open (n = 14), laparoscopic (n = 2)

1259.5NS
Frühling et al.,

2017 [49]

30 / 38HCC (n = 8),

CRLM (n = 23), other (n = 7); 2.4 cm

Percutaneous

(n = 30)

22,365.8

(at 6 months)

NS
Hosein et al.,

2014 [50]

28 / 58CRLM (n = 58),

2.7 cm

Percutaneous

(n = 28)

10,797NS
Kingham et al.,

2012 [51]

28 / 65HCC (n = 2),

CRLM (n = 21), other (n = 5); 1.0 cm

Percutaneous

(n = 6), open (n = 22)

693.8NS
Narayanan et al.,

2014 [52]

67 / 100HCC (n = 35),

CRLM (n = 20), CCC (n = 5); 2.7 cm

Percutaneous

(n = 67)

10,3NSNS
Niessen et al.,

2015 [53]

25 / 59HCC (n = 22),

CRLM (n = 16), CCC (n = 6), other (n = 4); 1.7 cm

Percutaneous

(n = 25)

670.8NS
Niessen et al.,

2016 [54]

34 / 59HCC (n = 33),

CRLM (n = 22), CCC (n = 5), other (n = 5); 2.4 cm

Percutaneous

(n = 34)

13,974.8NS
Niessen et al.,

2017 [55]

71 / 64HCC (n = 31),

CRLM (n = 16), CCC (n = 6), other (n = 4); 2.3 cm

Percutaneous

(n = 71)

35,768.3NS
Philips et al.,

2013 [56]

60 / 62HCC (n = 13),

CRLM (n = 23), CCC (n = 2), other (n = 22); 3.8 cm

Percutaneous

(NS) open (NS)

18NSNS
Scheffer et al.,

2014 [57]

10 / 10CRLM (n = 10),

2.4 cm

Open (n = 10)088.9NS
Thomson et al.,

2011 [58]

25 / 63HCC (n = 17),

CRLM (n = 15), other (n = 31); 2.5 cm

Percutaneous

(n = 25)

351.656.5

Hepatic IRE appears to be safe, even when performed near vessels and bile ducts [59] [60] with an overall complication rate of 16%, with most complications being needle related (pneumothorax and hemorrhage).The COLDFIRE-2 trial with 50 patients showed 76% local tumor progression-free survival after 1 year. [61] Whilst there are no studies comparing IRE to other ablative therapies yet, thermal ablations have shown a higher efficacy in that matter with around 96% progression free survival. Therefor Bart et al. [36] concluded that IRE should currently only be performed for only truly unresectable and non-ablatable tumors.

Pancreas

Table 2: Irreversible Electroporation Clinical Data in the Pancreas [36]
Author, YearNo. of

Patients

Stage of Disease

and Median Largest Tumor Diameter

ApproachMedian

Follow-up

(mo)

Median

Overall Survival (mo)

Local

Recurrence (%)

Tumor

Downstaging Caused by IRE

Belfiore et al.,

2017 [62]

29LAPC, NSPercutaneous2914.033 patients
Flak et al.,

2019 [63]

33LAPC, 3.0 cm

(88% after chemotherapy or radiation therapy)

Percutaneous

(n = 32), open (n = 1)

918.5 (diagnosis),

10.7 (IRE)

NS3 patients
Kluger et al.,

2016 [64]

50LAPC T4, 3.0 cmOpen8,712.0 (IRE)11NS
Lambert et al.,

2016 [65]

21LAPC, 3.9 cmOpen (n = 19),

percutaneous (n = 2)

NS10.2NSNS
Leen et al.,

2018 [66]

75LAPC, 3.5 cm (after

chemotherapy)

Percutaneous11.727.0 (IRE)383 patients
Månsson et al.,

2016 [67]

24LAPC, NS (after

chemotherapy)

PercutaneousNS17.9 (diagnosis),

7.0 (IRE)

582 patients
Månsson et al.,

2019 [68]

24LAPC, 3.0 cm (before

chemotherapy)

PercutaneousNS13.3 (diagnosis)330
Martin et al.,

2015 [69]

150LAPC, 2.8 cm (after

chemo- or radiation therapy)

Open2923.2 (diagnosis),

18 (IRE)

2NS
Narayanan

et al., 2016 [70]

50LAPC, 3.2 cm 6 1.3

(after chemo- or radiation therapy)

PercutaneousNS27 (diagnosis),

14.2 (IRE)

NS3 patients
Paiella et al.,

2015 [71]

10LAPC, 3.0 cmOpen7.615.3 (diagnosis),

6.4 (IRE)

NSNS
Ruarus et al.,

2019 [72]

50LAPC (n = 40)

and local recurrence (n = 10), 4.0 cm (68% after chemotherapy)

PercutaneousNS17.0 (diagnosis),

9.6 (IRE)

460 patients
Scheffer et al.,

2017 [73]

25LAPC, 4.0 cm

(52% after chemotherapy)

Percutaneous12 (7–16)17.0 (diagnosis),

11.0 (IRE)

NSNS
Sugimoto et al.,

2018 [74]

8LAPC, 2.9 cmOpen or

percutaneous, NS

17.517.5 (diagnosis)380 patients
Vogel et al.,

2017 [75]

15LAPC, NSOpen2416 (diagnosis)NSNS
Yan et al.,

2016 [76]

25LAPC, 4.2 cmOpen3NS2NS
Zhang et al.,

2017 [77]

21LAPC, 3.0 cmPercutaneous1NSNSNS

Animal studies have shown the safety and efficacy of IRE on pancreatic tissue. [78] The overall survival rates in studies on the use of IRE for pancreatic cancer provide an encouraging nonvariable endpoint and show an additive beneficial effect of IRE compared with standard-of care chemotherapeutic treatment with FOLFIRINOX (a combination of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) (median OS, 12–14months). [79] [80] However, IRE appears to be more effective in conjunction with systemic therapy and is not suggested as first-line treatment. [68] Despite that IRE makes adjuvant tumor mass reduction therapy for LAPC possible, IRE remains, in its current state, a high risk procedure requiring additional safety data before it can be used widely. [81]

Prostate

Table 3: Irreversible Electroporation Clinical Data in the Prostate [36]
Author, YearNo. of

Patients

Gleason ScorePretreatment or

Concurrent Treatment

Adverse events, 1/2/3/4/5Functional Outcome

(% of patients)

Oncologic Efficacy

(no. of patients)

Comments
Onik and Rubinsky

(2010) [82]

163+3: n = 7

3+4: n = 6

4+4: n = 3

NSNRAt 6 months:

urinary incontinence 0% erectile dysfunction 0%

Local recurrence, n = 0;

out-of-field occurrence, n = 1

Adequate flow in NVB postoperative
Van den Bos et al.

(2016) [83]

163+3: n = 8

4+3: n = 3

4+4: n = 2

Radical prostatectomy

4 weeks after IRE

15/8/1/0/0NS15 patients showed

complete fibrosis or necrosis of ablation zone

Electrode configuration completely enveloped ablation, leaving no viable cells in 15 patients
Van den Bos et al.

(2018) [84]

633+3: n = 9

3+4: n = 38

4+3: n = 16

Concurrent TURP (n = 10)Grade 1: 24%

Grade 2: 11%

Grade 3–5: 0%

At 12 months:

urinary incontinence 0%;

erectile dysfunction 23%

Local recurrence, n = 7;

out-of-field recurrence, n = 4

Safe and effective
Guenther et al.

(2019) [85]

429/4713+3: n = 82

3+4/4+3:

n = 225

4+4: n = 68

5+3/3+5: n = 3

>4+4 = 42

Pretreated with: radical

prostatectomy (n = 21),

radiation therapy (n = 28),

TURP (n = 17),

HIFU (n = 8)

ADT (n = 29)

93/17/7/0/0At >=12 months:

urinary incontinence 0%;

erectile dysfunction 3%

after up to 6y:

local recurrence, n = 20;

out-of-field recurrence, n = 27

Comparable 5-year Recurrence Free Survival to radical prostatectomy with improved urogenital outcomes
Valerio et al.

(2014) [86]

343+3: n = 9

3+4: n = 19

4+3: n = 5

4+4: n = 1

NS12/10/0/0/0At 6 months: urinary

incontinence 0%;

erectile dysfunction 5%

Local residual disease, n = 6;

only one histologic verification. Out-of-field recurrence, NS

Average ablation volume of 12mL
Ting et al.

(2016) [87]

253+3: n = 2

3+4: n = 15

4+3: n = 8

4+4: n = 0

NoneGrade 1: 35%

Grade 2: 29%

Grade 3–5: 0%

At 6 months: urinary

incontinence 0%;

erectile dysfunction, unknown

Local recurrence, n = 0;

out-of-fieldrecurrence, n = 5 (with histologic verification)

Good oncological control achieved with low toxicity
Blazevski et al. (2020) [88] 503+3: n = 5

3+4: n = 37

4+3: n = 6

4+4: n = 2

NSGrade 1: 10

Grade 2: 9

Grade 3–5: 0%

incontinence 2% (study only focused apical lesions);

erectile dysfunction 6%

Local recurrence, n=1

out-of-field recurrence, NS

Study only focused on apical lesions (difficult to treat with other methods without causing impotence and incontinence).

Focal ablation using IRE for PCa in the distal apex appears safe and feasible.

The concept of treating prostate cancer with IRE was first proposed by Gary Onik and Boris Rubinsky in 2007. [89] Prostate carcinomas are frequently located near sensitive structures which might be permanently damaged by thermal treatments or radiation therapy. The applicability of surgical methods is often limited by accessibility and precision. Surgery is also associated with a long healing time and high rate of side effects. [90] Using IRE, the urethra, bladder, rectum and neurovascular bundle and lower urinary sphincter can potentially be included in the treatment field without creating (permanent) damage.[ citation needed ]

IRE has been in use against prostate cancer since 2011, partly in form of clinical trials, compassionate care or individualized treatment approach. As for all other ablation technologies and also most conventional methods, no studies employed a randomized multi-center approach or targeted cancer-specific mortality as endpoint. Cancer-specific mortality or overall survival are notoriously hard to assess for prostate cancer, as the trials require more than a decade and usually several treatment types are performed during the years making treatment-specific survival advantages difficult to quantify. Therefore, the results of ablation-based treatments and focal treatments in general usually use local recurrences and functional outcome (quality of life) as endpoint. In that regard, the clinical results collected so far and listed in Table 3 shown encouraging results and uniformly state IRE as a safe and effective treatment (at least for focal ablation) but all warrant further studies. The largest cohort presented by Guenther et al. [85] with up to 6-year follow-up is limited as a heterogeneous retrospective analysis and no prospective clinical trial. Therefore, despite that several hospitals in Europe have been employing the method for many years with one private clinic even listing more than one thousand treatments as of June 2020, [91] IRE for prostate cancer is currently not recommended in treatment guidelines.

Kidney

While nephron-sparing surgery is the gold standard treatment for small, malignant renal masses, ablative therapies are considered a viable option in patients who are poor surgical candidates. Radiofrequency ablation (RFA) and cryoablation have been used since the 1990s; however, in lesions larger than 3 cm, their efficacy is limited. The newer ablation modalities, such as IRE, microwave ablation (MWA), and high-intensity focused ultrasound, may help overcome the challenges in tumor size. [92]

The first human studies have proven the safety of IRE for the ablation of renal masses; however, the effectiveness of IRE through histopathological examination of an ablated renal tumor in humans is yet to be known. Wagstaff et al. have set out to investigate the safety and effectiveness of IRE ablation of renal masses and to evaluate the efficacy of ablation using MRI and contrast-enhanced ultrasound imaging. In accordance with the prospective protocol designed by the authors, the treated patients will subsequently undergo radical nephrectomy to assess IRE ablation success. [93]

Later phase 2 prospective trials showed good results in terms of safety and feasibility [94] [95] for small renal masses but the cohort was limited in numbers (7 and 10 patients respectively), hence efficacy is not yet sufficiently determined. IRE appears safe for small renal masses up to 4 cm. However, the consensus is that current evidence is still inadequate in quality and quantity. [36]

Lung

In a prospective, single-arm, multi-center, phase II clinical trial, the safety and efficacy of IRE on lung cancers were evaluated. The trial included patients with primary and secondary lung malignancies and preserved lung function. The expected effectiveness was not met at interim analysis and the trial was stopped prematurely. Complications included pneumothoraces (11 of 23 patients), alveolar hemorrhage not resulting in significant hemoptysis, and needle tract seeding was found in 3 cases (13%). Disease progression was seen in 14 of 23 patients (61%). Stable disease was found in 1 (4%), partial remission in 1 (4%) and complete remission in 7 (30%) patients. The authors concluded that IRE is not effective for the treatment of lung malignancies. [96] Similarly poor treatment outcomes have been observed in other studies. [97] [98]

A major obstacle of IRE in the lung is the difficulty in positioning the electrodes; placing the probes in parallel alignment is made challenging by the interposition of ribs. Additionally, the planned and actual ablation zones in the lung are dramatically different due to the differences in conductivity between tumor, lung parenchyma, and air. [99]

Coronary arteries

Maor et el have demonstrated the safety and efficiency of IRE as an ablation modality for smooth muscle cells in the walls of large vessels in rat model. [100] Therefore, IRE has been suggested as preventive treatment for coronary artery re-stenosis after percutaneous coronary intervention.[ citation needed ]

Cardiac ablation therapy

Numerous studies in animals have demonstrated the safety and efficiency of IRE as a non-thermal ablation modality for pulmonary veins in the context of atrial fibrillation treatment. [101] In 2023, irreversible electroporation is being widely used and evaluated in humans, as cardiac ablation therapy to kill very small areas of heart muscle. This is done to treat irregularities of heart rhythm. A cardiac catheter delivers trains of high-voltage ultra-rapid electrical pulses that form irreversible pores in cell membranes, resulting in cell death. It is thought to allow better selectivity than the previous techniques, which used heat or cold to kill larger volumes of muscle. [102]

Other organs

IRE has also been investigated in ex-vivo human eye models for treatment of uveal melanoma [103] and in thyroid cancer. [104]

Successful ablations in animal tumor models have been conducted for lung, [105] [106] brain, [107] [108] heart, [109] skin, [110] [111] bone, [112] [113] head and neck cancer, [114] and blood vessels. [115]

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<span class="mw-page-title-main">Cryoablation</span> Process using extreme cold to destroy tissue

Cryoablation is a process that uses extreme cold to destroy tissue. Cryoablation is performed using hollow needles (cryoprobes) through which cooled, thermally conductive fluids are circulated. Cryoprobes are positioned adjacent to the target in such a way that the freezing process will destroy the diseased tissue. Once the probes are in place, the attached cryogenic freezing unit removes heat from ("cools") the tip of the probe and by extension from the surrounding tissues.

A paraneoplastic syndrome is a syndrome that is the consequence of a tumor in the body. It is specifically due to the production of chemical signaling molecules by tumor cells or by an immune response against the tumor. Unlike a mass effect, it is not due to the local presence of cancer cells.

Electrochemotherapy (ECT) is a type of chemotherapy that allows delivery of non-permeant drugs to the cell interior. It is based on the local application of short and intense electric pulses that transiently permeabilize the cell membrane, thus allowing transport of molecules otherwise not permitted by the membrane. Applications for treatment of cutaneous and subcutaneous tumors have reached clinical use by utilizing drugs such as bleomycin or cisplatin). Electrochemotherapy with bleomycin was used to treat a patient for the first time in 1991 at the Institute Gustave Roussy in France, while electrochemotherapy with cisplatin was used to treat for the first time in 1995 at the Institute of Oncology, Ljubljana, Slovenia. Since then, more than 4000 patients were treated with electrochemotherapy all over the world. Recently, new electrochemotherapy modalities have been developed for treatment of internal tumors using surgical procedures, endoscopic routes, or percutaneous approaches to gain access to the treatment area.

<span class="mw-page-title-main">Bone metastasis</span> Medical condition

Bone metastasis, or osseous metastatic disease, is a category of cancer metastases that result from primary tumor invasions into bones. Bone-originating primary tumors such as osteosarcoma, chondrosarcoma, and Ewing sarcoma are rare; the most common bone tumor is a metastasis. Bone metastases can be classified as osteolytic, osteoblastic, or both. Unlike hematologic malignancies which originate in the blood and form non-solid tumors, bone metastases generally arise from epithelial tumors and form a solid mass inside the bone. Bone metastases, especially in a state of advanced disease, can cause severe pain, characterized by a dull, constant ache with periodic spikes of incident pain.

Treatment for prostate cancer may involve active surveillance, surgery, radiation therapy – including brachytherapy and external-beam radiation therapy, proton therapy, high-intensity focused ultrasound (HIFU), cryosurgery, hormonal therapy, chemotherapy, or some combination. Treatments also extend to survivorship based interventions. These interventions are focused on five domains including: physical symptoms, psychological symptoms, surveillance, health promotion and care coordination. However, a published review has found only high levels of evidence for interventions that target physical and psychological symptom management and health promotion, with no reviews of interventions for either care coordination or surveillance. The favored treatment option depends on the stage of the disease, the Gleason score, and the PSA level. Other important factors include the man's age, his general health, and his feelings about potential treatments and their possible side-effects. Because all treatments can have significant side-effects, such as erectile dysfunction and urinary incontinence, treatment discussions often focus on balancing the goals of therapy with the risks of lifestyle alterations.

<span class="mw-page-title-main">Cone beam computed tomography</span> Medical imaging technique

Cone beam computed tomography is a medical imaging technique consisting of X-ray computed tomography where the X-rays are divergent, forming a cone.

<span class="mw-page-title-main">Cancer biomarker</span> Substance or process that is indicative of the presence of cancer in the body

A cancer biomarker refers to a substance or process that is indicative of the presence of cancer in the body. A biomarker may be a molecule secreted by a tumor or a specific response of the body to the presence of cancer. Genetic, epigenetic, proteomic, glycomic, and imaging biomarkers can be used for cancer diagnosis, prognosis, and epidemiology. Ideally, such biomarkers can be assayed in non-invasively collected biofluids like blood or serum.

<span class="mw-page-title-main">Sonodynamic therapy</span>

Sonodynamic therapy (SDT) is a noninvasive treatment, often used for tumor irradiation, that utilizes a sonosensitizer and the deep penetration of ultrasound to treat lesions of varying depths by reducing target cell number and preventing future tumor growth. Many existing cancer treatment strategies cause systemic toxicity or cannot penetrate tissue deep enough to reach the entire tumor; however, emerging ultrasound stimulated therapies could offer an alternative to these treatments with their increased efficiency, greater penetration depth, and reduced side effects. Sonodynamic therapy could be used to treat cancers and other diseases, such as atherosclerosis, and diminish the risk associated with other treatment strategies since it induces cytotoxic effects only when externally stimulated by ultrasound and only at the cancerous region, as opposed to the systemic administration of chemotherapy drugs.

Interventional oncology is a subspecialty field of interventional radiology that deals with the diagnosis and treatment of cancer and cancer-related problems using targeted minimally invasive procedures performed under image guidance. Interventional oncology has developed to a separate pillar of modern oncology and it employs X-ray, ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) to help guide miniaturized instruments to allow targeted and precise treatment of solid tumours located in various organs of the human body, including but not limited to the liver, kidneys, lungs, and bones. Interventional oncology treatments are routinely carried out by interventional radiologists in appropriate settings and facilities.

In the field of medicine, radiomics is a method that extracts a large number of features from medical images using data-characterisation algorithms. These features, termed radiomic features, have the potential to uncover tumoral patterns and characteristics that fail to be appreciated by the naked eye. The hypothesis of radiomics is that the distinctive imaging features between disease forms may be useful for predicting prognosis and therapeutic response for various cancer types, thus providing valuable information for personalized therapy. Radiomics emerged from the medical fields of radiology and oncology and is the most advanced in applications within these fields. However, the technique can be applied to any medical study where a pathological process can be imaged.

Damian E. Dupuy, M.D., F.A.C.R. is an adjunct professor of Diagnostic Imaging at Brown University's Warren Alpert Medical School and Director of Ablation services at Cape Cod Hospital. He is also a Member of Cape Cod preferred Physicians.

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