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Archive for the ‘Interventional Oncology: Radiofrequency Ablation, Transarterial Chemoembolization, Microwave Ablation and Irreversible Electroporation (IRE)’ Category


p53 mutation – Li-Fraumeni Syndrome – Likelihood of Genetic or Hereditary conditions playing a role in Intergenerational incidence of Cancer

 

Reporter: Aviva Lev-Ari, PhD, RN

 

THIS ARTICLE IS RECOMMENDED READING TO ALL OUR e-Readers

because it is a REAL story of a high school student fighting Brain Cancer, glioblastoma multiforme (GBM)

it presents the FRONTIER OF GENOMICS, PRECISION MEDICINE, Interventional Radiology and Interventional ONCOLOGY at

Stanford University, Canary Center at Stanford for Early Cancer Detection, Stanford Medical Center and Lucile Packard Children’s Hospital

I was exposed to Li-Fraumeni Syndrome in the following article:

‘And yet, you try’ – A father’s quest to save his son

http://stanmed.stanford.edu/2016fall/milan-gambhirs-li-fraumeni-syndrome.html

 

Li-Fraumeni syndrome

Other Names for This Condition

  • LFS
  • Sarcoma family syndrome of Li and Fraumeni
  • Sarcoma, breast, leukemia, and adrenal gland (SBLA) syndrome
  • SBLA syndrome

LFS is a rare disorder that greatly increases the risk of developing several types of cancer, particularly in children and young adults.

The cancers most often associated with Li-Fraumeni syndrome include breast cancer, a form of bone cancer called osteosarcoma, and cancers of soft tissues (such as muscle) called

Soft tissue sarcoma forms in soft tissues of the body, including muscle, tendons, fat, blood vessels, lymph vessels, nerves, and tissue around joints.


(small hormone-producing glands on top of each kidney). Several other types of cancer also occur more frequently in people with Li-Fraumeni syndrome.

A very similar condition called Li-Fraumeni-like syndrome shares many of the features of classic Li-Fraumeni syndrome. Both conditions significantly increase the chances of developing multiple cancers beginning in childhood; however, the pattern of specific cancers seen in affected family members is different.

Genetic Changes

The CHEK2 and TP53 genes are associated with Li-Fraumeni syndrome.

More than half of all families with Li-Fraumeni syndrome have inherited mutations in the gene. TP53 is a tumor suppressor gene, which means that it normally helps control the growth and division of cells. Mutations in this gene can allow cells to divide in an uncontrolled way and form tumors. Other genetic and environmental factors are also likely to affect the risk of cancer in people with TP53 mutations.

A few families with cancers characteristic of Li-Fraumeni syndrome and Li-Fraumeni-like syndrome do not have TP53 mutations, but have mutations in the CHEK2 gene. Like the TP53 gene, CHEK2 is a tumor suppressor gene. Researchers are uncertain whether CHEK2 mutations actually cause these conditions or are merely associated with an increased risk of certain cancers (including breast cancer).

Inheritance Pattern

Li-Fraumeni syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase the risk of developing cancer. In most cases, an affected person has a parent and other family members with cancers characteristic of the condition.

Diagnosis and Management

These resources address the diagnosis or management of Li-Fraumeni syndrome:

References on LFS

SOURCE

https://ghr.nlm.nih.gov/condition/li-fraumeni-syndrome

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Thriving Three Groups on LinkedIn

Groups Launcher and Group Manager: Aviva Lev-Ari, PhD, RN

 

Cardiovascular Biotech & Pharma UK & US Networking Group

918 members

https://www.linkedin.com/groups/4357927

 

 

Leaders in Pharmaceutical Business Intelligence

344 members

https://www.linkedin.com/groups/4346921

 

 

Innovation in Israel

190 members

https://www.linkedin.com/groups/2987122

 

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Low Energy Photon Intra-Operative Radiotherapy System

Larry H. Bernstein, MD, FCAP, Curator

LPBI

 

The Dosimetric Characteristics and Potential Limitation in Clinical Application of a Low Energy Photon Intra-Operative Radiotherapy System

Spring Zhou Editor at Scientific Research Publishing        https://www.linkedin.com/grp/post/143951-6069684489951391748

 

Purpose: To investigate the dosimetric characteristics of a low energy photon intra-operative radiotherapy (IORT) system and explore its potential limitation in clinical application.

Methods: A special water phantom, a parallel-plate ionization chamber and an electrometer were used to measure the depth dose rate, isotropy of dose distribution in X/Y plane, dosimetry reproducibility of bare probe and spherical applicators of different size which were used in comparison with the system data.

Results: The difference in depth dose rate between the measurement and system data for bare probe is -2.16% ± 1.36%, the range of the relative deviation for isotropy in the X/Y plane is between -1.9% and 2.1%. The difference in depth dose rate, transfer coefficient, isotropy in X/Y plane between the measurement and system data for the whole set of spherical applicators is -10.0% – 2.3%, -8.9% – 4.2% and -1.6% – 2.6%, respectively. Higher surface dose rate and steeper gradient depth dose are observed in smaller spherical applicators. The depth dose rate and isotropy for bare probe and spherical applicators have been shown good reproducibility. The uncertainty of measurement is associated with the positioning accuracy, energy response, noise current and correction function f’(R).

Conclusions: Thorough commissioning of the low energy photon IORT system helps us better understand the dosimetry characteristics, verify the system data, obtain adequate data for clinical application and routine quality assurance. The steep gradient depth dose and limited treatment range may restrain its potential in clinical application.

http://www.scirp.org/journal/PaperInformation.aspx?PaperID=56700&amp

 

The Dosimetric Characteristics and Potential Limitation in Clinical Application of a Low Energy Photon Intra-Operative Radiotherapy System

IJMPCERO> Vol.4 No.2, May 2015    DOI: 10.4236/ijmpcero.2015.42023

Zhenhua Xiao, Ouyang Bin, Zhenyu Wang, Botian Huang, Bixiu Wen*

 

Cite this paper

Xiao, Z. , Bin, O. , Wang, Z. , Huang, B. and Wen, B. (2015) The Dosimetric Characteristics and Potential Limitation in Clinical Application of a Low Energy Photon Intra-Operative Radiotherapy System. International Journal of Medical Physics, Clinical Engineering and Radiation Oncology, 4, 184-195. doi:10.4236/ijmpcero.2015.42023.
Intra-operative radiotherapy (IORT) delivers single high dose radiation directly to the tumor bed within a relative short period of treatment time during the surgical operation, which requires a higher surface dose to protect the deep normal tissues. It often uses high energy electron beam or low energy photon beam. Modern IORT is usually delivered in the operating room, which requires that the device is light weighted and easy to move with high quality of radiation protection. Dedicated IORT device commercially available includes Mobetron® MeV electron beam system [1] (Intra Op Medical Corporation, California, USA), NOVAC™ 7 system (New Radiant Technology SpA, Italy) and the INTRABEAM® 50 kV X-ray device (Carl Zeiss Medical Company, Germany).
Since the results from the randomized TARGIT A trial were published, IORT has been applied for locally advanced or recurrent rectal cancer [2], superficial cutaneous malignancies [3] and as full dose partial breast irradiation (PBI) or as a boost after whole-breast radiatherapy (WBI) in early stage breast cancer [4] [5]. Vaidya J.S. et al. have analysis overall survival of using as single-dose targeted intraoperative radiotherpay (TARGIT) versus fractionated external beam radiotherapy (EBRT) for breast cancer. For patients enrolled at 33 centers in 11 countries, 1721 patients were randomised to TARGIT and 1730 to EBRT. The 5-year risk for local recurrence in the conserved breast was 3.3% (95% CI 2.1 – 5.1) for TARGIT versus 1.3% (0.7 – 2.5) for EBRT (p = 0.042). Wound-related complications were much the same between groups but grade 3 or 4 skin complications were significantly reduced with TARGIT (four of 1720 vs 13 of 1731, p = 0.029) [6]. TARGIT-B (for boost, ISRCTN43138042) is an ongoing multicenter randomised controlled trial that began in 2013, which is testing the replacement of EBRT boost to the tumor bed by a TARGIT boost given during surgery. An ongoing open registry study, TARGIT-R (for registry, ISRCTN91179875), began in 2013, aiming to monitor the long-term effectiveness and safety of the patients treated with TARGIT following breast conserving surgery for early breast cancer [7].
Eaton D.J. et al. described the dosimetry of the INTRABEAM® system with the spherical applicators [8]. Maxime Goubert et al. have reported dosimetric behavior of the system equipped with flat and surface applicators [3]. There still remains controversary for the dosimetric characteristics and clinical application of IORT. In this paper we introduce the commissioning test of the INTRABEAM® 50 kV x-ray system by investigating the dosimetric characteristics of the low energy photon IORT system and explore its potential limitation in clinical application.
……
The device for measurement includes a dedicated water tank (see in Figure 1) with radiation protection design (Carl Zeiss Surgical GmbH), a parallel plate ionization chamber (volume: 0.0053 cm3, type 34013, PTW, Freiburg, Germany) and a dosimeter (UNIDOS E, PTW). Two waterproof measuring chambers in the water tank were designed to measure depth dose rate and isotropy respectively. The ionization chamber(IC) is inserted with the ionization holder into the measuring chamber, which is closed with cover during measurement. “dIC” is designated as “distance between the entrance foil and chamber top” in PTW calibration certificate. The thickness of measuring chamber was printed in the user manual as “dH”. The air gap “dA” between the upper surface of ionization chamber housing and the inside of measuring chamber wall is constantly 0.5 mm. Those distances are considered in measuring the depth dose rate at particular position. The XRS is fixed into the platform which can be adjusted vertically with range of 10 cm and precision of 0.001 mm. The lowest surface of the probe was defined as the isocenter of 0 mm in depth. Due to the certain thickness of the holder wall of the ionization chamber, the measurement in Z direction ranges from 2.0 mm to 44.0 mm with 0.5 mm increment when the distance is less than 40.0 mm, 1.0 mm for 40.0 mm or higher with a period of 1 minute for each point of measurement. The platform of the water tank is also designed with a turntable structure in the X/Y plane for measuring the isotropic dose distribution. The XRS can be rotated with the platform every 45˚ to the total of 8 angles (initial position was defined as 0˚ during measurements). The X, Y directions can be located by fine tune to align the central axis of the bare source probe with the center of the ionization chamber. The position of X, Y directions were kept unchanged for isotropic measurement.
……
3.1. Depth Dose Rate of Bare Probe The depth dose rate for the bare probe was measured three times. Figure 2 depicts the dose rate in Gy/min or error of measurement in percentage as a function of distance between the surface of XRS probe and the ionization chamber monitor-node. The red line represents the average measurement for three times, the data in blue line are obtained from the operation system and the repeatability of the measurements for 3 times are shown in percentage of error in black line. As shown in Figure 2(a) & Figure 2(b), the maximum deviation of three times measurement for bare probe ranges from 0.14% to 1.3%. The value of dose rate measured is higher than that obtained from the operation system when the distance between the surface of XRS probe to the ionization chamber monitor-node is <5.0 mm; the value measured is lower than that from the operation system when the distance is 10.0 mm or more. The average error between the actual measurement and the system is −2.16% ± 1.36% ranging from −3.65% to 2.83%.
3.2. Isotropy of Bare Probe Figure 3(a) depicts isotropic dose in X/Y plane for bare probe, the value of each angle was normalized to the average of 8 measurements at the specific distance. The consistency for the value of each measurement angle is relatively good. As shown in Figure 3(b), the relative deviation of measurements for four times ranged from −1.9% to 2.1%. The deviation of measurement at 90˚ (−1.9%) and 225˚ (2.1%) were relatively larger. The tendency of the measuring error is consistent with good repeatability.
Figure 1. Schematic diagram of commissioning setup for a spherical applicator of 4.5 cm in diameter (water tank).
Figure 2. The depth dose rate (a) and the error in percentage; (b) measured in comparison with data from operation system for bare probe. The red line represents the average of measurement for three times, blue line depicts the data from the operation system, the black line for the deviation of measurement with bare probe in percentage error.
Figure 3. Isotrophy in X/Y plane for bare probe. (a) Normalized value and relative deviation in 8 measurement angles. The hollow circle represents the normalized value, and solid dots the relative percentage deviation of each measurement point magnified 20 times; (b) Relative percentage deviation for 4 times measurement.
3.3. Depth Dose Rate of Spherical Applicators Figure 4(a) depicts the curve of dose rate measured as a function of the distance from the surface of spherical applicators to ionization chamber monitor-node for 8 types of spherical applicators. The dose rate is the highest at the surface of the applicators which falls as the distance between the surfaces of spherical applicators to ionization chamber monitor-node increases. The dose rate varies significantly with the size of the applicator. For the applicator with smaller diameter the dose rate is higher with relative shorter treatment time if the same radiation dose is delivered. As the diameter of the applicator increases, the falling gradient in dose rate slows down. From Figure 4(a), we also observe that the curves of the dose rate overlaps for applicators in diameters 2.5 cm and 3.5 cm, 3.0 cm and 4.0 cm, respectively.
Figure 4(b) shows the curve of depth dose rate as a function of distance between the isocenter of spherical applicator and ionization chamber monitor-node. Obvious separation of dose rate was observed. At the same distance from the isocenter, the dose rate is smaller in the applicators of diameter ≤3.0 cm than those of diameter >3.0 cm. The difference in depth dose rate, transfer coefficient and isotropy between measurements and system data is presented in Table 1. The average deviation in depth dose rate between measurements and system data for the applicators of diameter ≤3.0 cm is in the range from −5.1% to −4.8%; it reduces to −2% – −0.1% with the increase in diameter of the applicators.
Figure 4. The curve of depth dose rate measured for each spherical applicator. (a) The curve of depth dose rate of different distance from the surface of spherical applicators to ionization chamber monitor-node; (b) The curve of depth dose rate of different distance from the isocenter of spherical applicator to ionization chamber monitor-node.
Table 1. The difference in depth dose rate, transfer coefficient and isotropy for spherical applicators.
Diameters (cm)   ……
Deviation of depth dose rate (range) (%) ……
Deviation of transfer coefficiency (range) (%) …….
Isotropy (range) (%) …….
3.4. Transfer Coefficient of Spherical Applicators The transfer coefficient of spherical applicator is defined as ratio between the depth dose rates with or without applicator at the same distance to the source isocenter. The depth dose rate can be obtained by multiplication of the bare source dose rate and the conversion coefficient. Figure 5 is the curve for deviation in transfer coefficient between measured values and the system data for spherical applicators. The average deviation of transfer coefficient at the same distance between the isocenter of spherical applicator and ionization chamber monitor-node for applicators ≤3.0 cm ranges from −2.6% to −2.2%; whereas the average deviation for tors >3.0 cm is between 0.8% and 2.4%. The more detailed data for difference in transfer coefficient between measurements and system data are presented in Table 1 for each individualized applicator.
3.5. Isotropy of Spherical Applicator As shown in Table 1, the average deviation in isotropy between measurements and system data of different spherical applicator’s X/Y plane ranges from −1.4% to 2.6% which shows no obvious change as the diameter of applicator increases. Figure 6(a) & Figure 6(b) depicts the representative isotropy for dose distribution in X/Y plane for a spherical applicator of diameter 4.5 cm which shows the consistency of the measurement values.
Figure 5. The curve for deviation in transfer coefficient between measured values and the system data for spherical applicators.
Figure 6. The representative isotropy in X/Y plane for a ϕ 4.5 cm spherical applicator. (a) Point view of normalized value and the relative deviation; (b) The percentage relative deviation of 3 times measurements.
3.6. Repeatability of Spherical Applicator The Dose rate was measured in 3 times for 4.5 cm spherical applicator, the deviation in repeatability ranges from 0.2% to 0.7%, which shows good repeatability and it gradually gets better as the depth increases. As shown in Figure 7(a) & Figure 7(b), poorer repeatability and increased deviation of error are observed when the distance >15 mm from the surface.
Figure 7. The curve for measurement value of depth dose rate and comparison chart with system data for ϕ 4.5 cm spherical applicator. (a) The depth dose rate for ϕ 4.5 cm spherical applicator. The red line intends for the average 3 measurement values, the blue line for the system value; (b)The error in percentage for the measurements in 3 times.
3.7. Potential Limitation of Clinical Application Figure 8 depicts the graphic of dose distribution for the spherical applicator in diameter 4.5 cm. The doses measured at the distance of 0.2, 0.5, 1.0, and 2.0 cm are 15.3, 10.7, 6.4 and 2.7 Gy, respectively when surface dose of 20 Gy is prescribed. Table 2 lists the depth dose value for spherical applicators when the surface dose of 20 Gy is prescribed, which shows fast dose falling with gradual increasing depth. The doses range from 35.0% to 56.0% at 5 mm from the surface of the spherical applicators and fall to 16.5% – 34.0% at 10 mm and 5.5% – 15.5% at 20 mm.
Figure 8. Dose distribution for a ϕ 4.5 cm spherical applicator when the surface dose of 20 Gy is prescribed.
Table 2. Depth dose rate (Gy) at serial typical depths for spherical applicators when surface dose of 20 Gy is prescribed.
Diameter (cm)
Distance from surface (mm) 0 2 5 10 15 20
Dose measurement tools used for INTRABEAM system include water tank/ionization chamber [10] [11], film/ solid water phantom [11], Thermo-luminescence [12], etc. Water tank/ionization chamber has the highest accuracyamong those instruments [13]. Schneider et al. have compared homogeneity of each dose distribution and depth-dose measurements for flat and surface applicators using film dosimetry in a solid water phantomand a soft X-ray ionization chamber in a water tank [10]. One of the important factors influencing the accuracy of the measurement is the relative position error of X-ray source to ionization chamber due to sharp attenuation of low energy X-ray in the water. The minimal position change will lead to relatively large measurement deviation. As shown in depth dose rate curve fitting function and differential coefficient data, the dose gradient at 3 and 10 mm from the source isocenteris 60%/mm and 24%/mm, respectively. The position error of ±0.1 mm will lead to deviation of dose rate at ±6% and ±2.4%, respectively.
Eaton et al. have reported that the positioning of X-ray source is the most important factor that affects the measurement result and the measurement accuracy may be affected by the ionization chamber’s volume effects in the area of steep dose falling, which may account for the poorer repeatability of measurement near the isocenter [13]. Other factors influence the accurate measurement including the energy response of ionization chamber [13], low voltage of X-ray [14], etc. The spectrum of X-ray approaching to the surface of the probe is complex ranging from 0 to 50 kV with a large number of low energy kV X-ray [14] (<20 kV) which showed rapid attenuation in water [15] resulting in significant difference at different depth and the measurement deviation could reach to ±2.2% due to the energy response [9].
Another important reason for poor repeatability is that the measurement can be affected by noise current. The sensitive volume of ionization chamber is only 0.0053 cm3, and the ionization chamber is supposed to collect only approximately 25 pC charge per minute at the depth of 35 mm during the measurement of X-ray source, which has led to low signal-to-noise ratio influenced by noise current. The uncertainty of measurement for ionization chamber could reach to ±3.4% [9]. The accuracy and repeatability of measurement will gradually decrease with further increase in the distance from the X-ray source since ionization chamber collects less charge per minute (about 16.5 pC).
The type of ionization chamber, design of measuring chamber for water tank, method for calculation and condition of acquisition system for absorbed dose are different between users and company system. The calculation of absorbed doses, transfer coefficient and isotropy in X/Y plane for the measurement data requires the manufacturer to provide the correction function f'(R) for bare probes and spherical applicators of different size. The f'(R) value is different at different depth which may introduce correction error, the error for uncertainty of f'(R) is relatively larger when the depth is shallower. The average of uncertainty for f'(R) is ±7.8%.
Armoogum et al. analyzed the factors that affect the measurement result including temperature and atmospheric pressure correction factor, ionization chamber position deviation, ionization chamber current, the chamber/dosimeter calibration factor, output drift and calibration of absorbed dose [9]. Among these factors positional deviation is the most significant one. The estimation of total uncertainty for all these factors can reach to ±10.8%. Our data have shown that deviation between the measurement data and the system ranges from −10.0% to −5.0% for spherical applicator ≤3 cm in diameter and within ±5.0% for the applicators>3 cm in diameter, which are comparable with the data reported in literatures [9].
Our data have also shown a relative larger deviation of isotropy in X/Y plane measured at 90˚ (1.9%) and 225˚ (2.1%). The possible reasons include: 1) the probe is a hollow needle with 100 mm long and 3.2 mm outside diameter which may be bended during the operation with need to be calibrated before each use since system requirements of probe bending value is less than 0.1 mm; 2) there may exist certain errors during the rotation of the water tank platform, which may lead to different distance from the tip of the probe to the ionization chamber monitor units in different angles; 3) the noise current may influence the correct measurements (the dosimeter charge is about 16.5 pC/min without applicators).
The clinical application of IORT with INTRABEAM system is determined by the size and category of applicators. The biggest diameter for spherical and tablet applicators is 5.0 cm and 6.0 cm, respectively. The surrounding wall is embedded with thin metal sheath interiorly for spherical applicators of diameter ≤3 cm. Low energy X-ray can be attenuated rapidly through the metal sheath. The gradient of dose rate value for spherical applicators in diameter ≤3 cm were larger than that for applicators with diameter >3cm when measured at the same distance from the isocenter.
Our results have shown that the steep dose gradient exists from 0 cm, the surface of the applicator to 1.0 cm; the higher surface dose rate and the greater dose gradient have been observed for the smaller applicators. When the region of treatment is too large, it will be very difficult to calculate accurate dose distribution due to lack of beam bridging technology with over- or under-dose. The limited region and depth of treatment may restrain from its potential in clinical application. Vaidya JS et al. have reported in TARGIT A, a phase III clinical trial that for patients with early breast cancer <2 cm the tumor local control rate of IORT is not inferior to external beam radiotherapy after breast conserving surgery; external beam radiotherapy should be considered for patients with tumor of 2 – 3 cm or with poorer prognostic factors [6]. Sperk E et al. have reported that patient selection for IORT should be restrictive when provided as accelerated partial breast irradiation (APBI) [4].
The system only uses water for dose calculation whereas homogeneity of human structure cannot be revised. The calculated dose value and the deviation will be very big in different tissue due to the spectrum chacteristics of the low energy photon (≤50 kV); the dose distribution will be influenced by the air gap between tissues and the applicator [14]. Monte Carlo modelling could be used in comparison with result from ionization chambers, radiochromic film and other dosimeters such as TLDs on the subsequent periodic QA tests for the INTRABEAM system [8]. There exist great difficulties for external beam radiotherapy when needed to supplement the postoperative radiotherapy especially for the accurate dose calculation and precise delineation of target and surrounding normal tissue irradiated especially for the nerves and blood vessels. All these factors mentioned above may seriously restrict INTRABEAM system to be widely used in clinical practice.
5. Conclusion In summary, thorough commissioning of INTRABEAM system helps us better understand the dosimetry characteristics, verify the system data and a quire adequate data for clinical application and routine quality assurance. It is necessary to establish the benchmark for long term quality assurance based on the measurement data. The characteristics of high dose at the surface of applicator, great dose gradient and limited treatment range may restrain from its potential in wide clinical application

References

[1] Beddar, A.S. (2005) Stability of a Mobile Electron Linear Accelerator System for Intraoperative Radiation Therapy. Medical Physics, 32, 3128-3131.   http://dx.doi.org/10.1118/1.2044432
[2] Klink, C.D., Binnebosel, M., Holy, R., Neumann, U.P. and Junge, K. (2014) Influence of Intraoperative Radiotherapy (IORT) on Perioperative Outcome after Surgical Resection of Rectal Cancer. World Journal of Surgery, 38, 992-996.    http://dx.doi.org/10.1007/s00268-013-2313-1
[3] Goubert, M. and Parent, L. (2015) Dosimetric Characterization of INTRABEAM((R)) Miniature Accelerator Flat and Surface Applicators for Dermatologic Applications. Physica Medica, 31, 224-232. http://dx.doi.org/10.1016/j.ejmp.2015.01.009
[4] Sperk, E., Astor, D., Keller, A., Welzel, G., Gerhardt, A., Tuschy, B., et al. (2014) A Cohort Analysis to Identify Eligible Patients for Intraoperative Radiotherapy (IORT) of Early Breast Cancer. Radiation Oncology, 9, 154.
http://dx.doi.org/10.1186/1748-717X-9-154
[5] Sedlmayer, F., Reitsamer, R., Fussl, C., Ziegler, I., Zehentmayr, F., Deutschmann, H., et al. (2014) Boost IORT in Breast Cancer: Body of Evidence. International Journal of Breast Cancer, 2014, Article ID: 472516.
http://dx.doi.org/10.1155/2014/472516
[6] Vaidya, J.S., Wenz, F., Bulsara, M., Tobias, J.S., Joseph, D.J., Keshtgar, M., et al. (2014) Risk-Adapted Targeted Intraoperative Radiotherapy versus Whole-Breast Radiotherapy for Breast Cancer: 5-Year Results for Local Control and Overall Survival from the TARGIT—A Randomised Trial. Lancet, 383, 603-613.    http://dx.doi.org/10.1016/S0140-6736(13)61950-9
[7] Williams, N.R., Pigott, K.H., Brew-Graves, C. and Keshtgar, M.R. (2014) Intraoperative Radiotherapy for Breast Cancer. Gland Surgery, 3, 109-119.
[8] Eaton, D.J. and Duck, S. (2010) Dosimetry Measurements with an Intra-Operative X-Ray Device. Physics in Medicine and Biology, 55, N359-N369.    http://dx.doi.org/10.1088/0031-9155/55/12/N02
[9] Armoogum, K.S., Parry, J.M., Souliman, S.K., Sutton, D.G. and Mackay, C.D. (2007) Functional Intercomparison of Intraoperative Radiotherapy Equipment—Photon Radiosurgery System. Radiation Oncology, 2, 11.
http://dx.doi.org/10.1186/1748-717X-2-11
[10] Schneider, F., Clausen, S., Tholking, J., Wenz, F. and Abo-Madyan, Y. (2014) A Novel Approach for Superficial Intraoperative Radiotherapy (IORT) Using a 50 kV X-Ray Source: A Technical and Case Report. Journal of Applied Clinical Medical Physics, 15, 4502.
[11] Ebert, M.A., Asad, A.H. and Siddiqui, S.A. (2009) Suitability of Radiochromic Films for Dosimetry of Very-Low Energy X-Rays. Journal of Applied Clinical Medical Physics, 10, 2957.    http://dx.doi.org/10.1120/jacmp.v10i4.2957
[12] Soares, C., Drupieski, C., Wingert, B., Pritchett, G., Pagonis, V., O’brien, M., et al. (2006) Absorbed Dose Measurements of a Handheld 50 kVP X-Ray Source in Water with Thermoluminescence Dosemeters. Radiation Protection Dosimetry, 120, 78-82.    http://dx.doi.org/10.1093/rpd/nci622
[13] Eaton, D.J. (2012) Quality Assurance and Independent Dosimetry for an Intraoperative X-Ray Device. Medical Physics, 39, 6908-6920.   http://dx.doi.org/10.1118/1.4761865
[14] Ebert, M.A. and Carruthers, B. (2003) Dosimetric Characteristics of a Low-kV Intra-Operative X-Ray Source: Implications for Use in a Clinical Trial for Treatment of Low-Risk Breast Cancer. Medical Physics, 30, 2424-2431.
http://dx.doi.org/10.1118/1.1595611
[15] Ebert, M.A., Carruthers, B., Lanzon, P.J., Haworth, A., Clarke, J., Caswell, N.M., et al. (2002) Dosimetry of a Low-kV Intra-Operative X-Ray Source Using Basic Analytical Beam Models. Australasian Physical Engineering Sciences in Medicine, 25, 119-123.   http://dx.doi.org/10.1007/BF03178772

 

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State-of-the-Art Procedures in Interventional Oncology –

Curator; Larry H. Bernstein, MD, FCAP

LPBI

Vascular and Interventional Radiology

http://www.hopkinsmedicine.org/vascular/conditions/oncology_interventional.html

Oncology

The Johns Hopkins interventional radiology physicians play a critical role as part of the Cancer Center team. Ours is a rapidly evolving field where innovative techniques for both diagnosing and treating cancer are now available resulting in prolonged quality survival for patients with cancer.

Therapeutic Procedures

  • Tumor ablation
    • Cryoablation
    • Radiofrequency ablation (RFA)
    • Microwave ablation

Supportive Procedures

  • Paracentesis or Thoracentesis
  • PICC line placement
  • Tunneled catheter placement
  • Port catheter placment
  • Percutaneous biliary drainage
  • Percutaneous nephrostomy
  • Pleurx catheter placement
  • Stenting of malignant strictures: bile duct, esophageal, tracheobronchial and intestinal
  • Portal vein embolization

Interventional Oncology

Interventional oncology, practiced by interventional radiologists, is one of four parts of a multidisciplinary team approach in the treatment of cancer and cancer related disorders. The others  include medical oncology, surgical oncology and radiation oncology.

Interventional oncology procedures provide minimally invasive, targeted treatment of cancer. Image guidance is used in combination with the most current innovations available to treat cancerous tumors while minimizing possible injury to other body organs. Most patients having these procedures are outpatients or require a one night stay in the hospital.

  • Some of these therapies are regional, as when treating cancers involving several areas of the liver with chemoembolization or radioembolization.
  • Others are better classified as local, as when treating focal lesions in the kidney, liver, lung and bone with cryoablation (freezing), or microwave or radiofrequency ablation (heating).

In general, these techniques are reserved for patients whose cancer cannot be surgically removed or effectively treated with systemic chemotherapy. These procedures are also frequently used in combination with other therapies provided by other members of the cancer team.

Burgeoning Field of Interventional Oncology Is Poised for Takeoff

A Q&A With Dan Brown, MD –

http://www.onclive.com/publications/obtn/2013/November-2013/Burgeoning-Field-of-Interventional-Oncology-Is-Poised-for-Takeoff-A-QandA-With-Dan-Brown-MD#sthash.qeToPGBm.dpuf

Andrew J. Roth @andrewjohnroth

Interventional oncology is an emerging field in cancer care that is intended to complement existing treatment modalities. We sat down with Dan Brown, MD, the new chief of Interventional Oncology at Vanderbilt University Medical Center, to discuss the burgeoning field and its potential effect on cancer care moving forward.

OBTN: What is interventional oncology and how does it fit in with the current cancer treatment paradigm?

Dr. Brown: Interventional oncology uses image-guided technology to directly target solid tumors. It’s a complementary intervention that I hope will eventually be integrated into standard care algorithms. It gives clinicians another focused area of cancer care in which we can collaborate with other specialists. We perform targeted procedures that can be characterized as either arterial or ablative. Interventional oncology, and to some extent interventional radiology, also involves the use of biopsies for genomics analysis, in a similar way as other oncologic specialists use biopsies to help guide their biological therapies or systemic therapies.

Which patients are likely candidates for interventional oncology and how are they identified?

Vanderbilt is the second place in the country to have a formal division of interventional oncology and a backbone of our program is tumor boards. I participate in at least three tumor boards a week involving specialists in gastrointestinal oncology, liver transplantation, and neuroendocrine tumors.

The cornerstone tumor for interventional oncology is probably hepatocellular carcinoma. Chemoembolization is one of the older procedures that we perform dating back to 1980. And it became standard of care because, quite frankly, there was nothing else for years that did anything. Now we perform it very frequently. We see this in the transplant population or potential transplant population— we want to prevent patients from progressing beyond Milan criteria or to try to downstage patients back to Milan criteria if they’re beyond it.

In patients with colorectal cancer, we can either try to get a patient to surgery with portal vein embolization or we will perform radioembolization of liver metastases or ablation of liver metastases based on where they stand with their chemotherapy. If patients get toxicity from chemotherapy, particularly neurotoxicity after FOLFOX, and have residual liver disease, sometimes we treat them to give them time off of systemic therapy.

We treat a lot of patients with neuroendocrine tumors here at Vanderbilt. We perform radioembolization and bland embolization for those patients. For patients with hepatocellular and colorectal metastases, our first goal is to get them to surgery, either transplant or resection, as these treatments are potentially curative.

Can you discuss in detail some of the procedures involved with interventional oncology?

There are two main techniques that we perform— arterial interventions and ablation. For liver cancer, arterial treatment involves threading a catheter through the femoral artery to reach the primary tumor (Figure 1). The strategy is to use the tumor’s vasculature to deliver microscopic beads that contain radioactive materials or chemotherapy into the tumor. The beads leach out the chemotherapy over the course of several weeks.

Figure 1. Hepatocellular carcinoma in a poor surgical candidate. The goal was to limit progression of disease through arterial intervention to allow transplant.

Dan-Brown-figure1 hepatocellular CA

Dan-Brown-figure1 hepatocellular CA

http://www.onclive.com/_media/_upload_image/Dan-Brown-figure1.jpg

a. 3-cm mass in the right lobe of the liver.

b. Catheter selecting the artery supplying the mass with enhancement of the tumor.

c. Complete tumor necrosis at follow-up imaging.

We can also infuse radioembolics in a similar way. There are two devices available—one is made of glass and the other is made of resin. In our practice, we’re treating more and more people with the radioembolic treatment because it’s an outpatient procedure. We’re starting to accumulate more data using the radioembolic treatment, especially for colon cancer and neuroendocrine tumors.

Radiofrequency ablation involves delivering an electrode into a tumor and passing a current through it. This raises the temperature in the tumor to about 60° Celsius, and kills it. Microwave ablation is a newer method used to destroy tumors with heat. It’s much more powerful, but its use is not as widespread. Finally, we can freeze tumors with cryoablation (Figure 2); this method will destroy tumor cells or regular noncancerous cells as well. Cryoablation is favored in small kidney masses, because the clinician can see the ice ball when it’s created. This has been very successful, and causes less pain than ablation that uses heat. And all these ablation types can be used in the kidney.

Figure 2. Renal cell carcinoma undergoing cryoablation in a patient who is not eligible for surgery.

Dan-Brown-figure2 RCC

Dan-Brown-figure2 RCC

http://www.onclive.com/_media/_upload_image/Dan-Brown-figure2.jpg

a. 3.5-cm left renal mass at baseline.
b. Ice ball at the end of CT-guided cryoablation.
c. Complete tumor necrosis 4 years after treatment.

We’ve seen a shift toward more radioembolization use. One product approved for treating hepatocellular carcinoma is TheraSphere, an FDA approved microsphere agent. SirSpheres are FDA approved for use in colorectal cancer with adjuvant chemotherapy. There are a number of prospective randomized trials going on worldwide that combine its use with first- and second-line chemotherapy regimens, and some of the first of those is called SIRFLOX. The study is designed to evaluate whether FOLFOX chemotherapy in combination with Selective Internal Radiation Therapy is more effective than chemotherapy alone. That should have data coming out some time next spring, when the data are mature enough to start analyzing.

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Peter Mueller, MD  Professor of Radiology @MGH & HMS – 2015 Synergy’s Honorary Award Recipient

Reporter: Aviva Lev-Ari, PhD, RN

Synergy Announces the Honorary Award Recipient for 2015

Synergy 2015 Honors

Peter Mueller, MD

Professor of Radiology

Division Head, Interventional Radiology

Massachusetts General Hospital

Harvard Medical School

Boston, MA

Peter Mueller, MD

Peter Mueller, MD

Peter Mueller completed his medical training at the University of Cincinnati, Ohio, USA. After that he was a resident in radiology at Massachusetts General Hospital, Department of Radiology, Boston, USA. In 1978 he started his interventional career in the GI radiology section at Massachusetts General Hospital. His mentor at that time was Joseph Ferrucci. Many of the procedures in non-vascular radiology, which are now considered routine, such as

  • percutaneous biopsy,
  • abscess drainage,
  • cholecystostomy,
  • gastrostomy,
  • biliary drainage,
  • benign biliary drainage and
  • percutaneous ablation of liver and renal tumours,

were either developed or further studied by the group of interventional radiologists that worked in this division. In the 1970s, 80s and 90s, the combination of imaging and intervention was just beginning and Prof. Mueller and his colleagues wrote many papers and gave many courses in these areas. His primary clinical and research interests are in interventional radiology, especially in biliary intervention, abscess drainage and percutaneous ablation of malignant tumours of the liver and kidney.

Over the years, Prof. Mueller has been intimately involved with novel techniques such as the Brown-Mueller T-Tack for use in percutaneous gastrostomy and percutaneous gastrojejunostomy and the Dawson-Mueller drainage catheter for fluid drainages. He has published well over 300 articles, several books and editorships, and given over 20 “named” lectures on interventional radiology. His Division of Abdominal Imaging and Interventional Radiology at Massachusetts General Hospital was one of the first in the United States to accept fellows from Europe, many of whom have gone on to distinguished careers in their homeland. This includes the recent President of CIRSE, Michael J. Lee.

More recently, he has become the Division Head of all Interventional Radiology at the MGH.

Prof. Mueller has been on the editorial boards of many radiology journals including

  • Radiology,
  • The American Journal of Roentgenology,
  • Clinical Radiology, and
  • Cardiovascular and Interventional Radiology.

He is the past Editor-in-Chief of Seminars in Interventional Radiology. He is the past President of the Society of Hepatobiliary Radiology, the New England Roentgen Ray Society, and the Society of Abdominal Radiology.

He has received an Honorary Membership of the European Society of Interventional Radiology and the European Radiology Society, Irish College of Medicine, the British College of Medicine and the Asian Society of Radiology.

He has received the Gold Medal from the British Interventional Radiology Society, and the Cardiovascular and Interventional Society of European Radiology (CIRSE); In addition, he has given the prestigious Dotter Lecture for the American Society of Interventional Radiology.

This year, Synergy honors Professor Mueller for his outstanding achievement and contribution to the field of Interventional Radiology.

 

SOURCE

From: Interventional Oncology 360 <newsletters@InterventionalOncology360.com>

Reply-To: <newsletters@InterventionalOncology360.com>

Date: Thursday, September 24, 2015 at 2:03 PM

To: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>

Subject: Synergy Announces the Honorary Award Recipient for 2015

Synergy 2015 – A Multidisciplinary Approach to Interventional Oncology

November 5-8, 2015, Eden Roc Hotel, Miami Beach, FL

This annual symposium offers attendees a review of a variety of oncological diseases combined with the latest developments in medical, interventional and surgical therapeutic options across multiple disciplines. A practical overview of how to incorporate emerging therapies into practice will be included with emphasis on the multidisciplinary approach needed to achieve the highest levels of success in the fight against cancer. New this year, is a one-day multidisciplinary symposium on Prostate Interventions (PAE) offering a comprehensive review on emerging topics and various aspects of Prostate Artery Embolization, combined with the latest developments in medical, surgical and interventional management of Benign Prostatic Hyperplasia and Prostate cancer. Leading experts from national and international programs will present the latest data and treatment innovations for oncological challenges in multiple organ systems with emphasis on implementation from diagnosis to treatment. The meeting will be didactic and interactive with panel discussions and instructive case presentations focused on hepatocellular carcinoma, lung cancer, metastatic colorectal cancer, cholangiocarcinoma and liver metastases, renal and prostate cancer, pancreatic cancer, neuroendocrine, musculoskeletal tumors and palliative treatment options. A Nursing Symposium will also be presented on the last day of the conference.

 

Statement of Need

In the past few years, interventional oncology has evolved into an important subspecialty as more interventional radiologists are actively involved in the management of oncologic patients. Unlike other procedures handled by interventional radiologists, interventional oncology requires an in-depth understanding of the different types of cancers, current standards and proper use of treatment choices and working with a multidisciplinary group. Synergy 2015 will be a forum for the convergence of the expertise and knowledge of various specialists involved in oncologic care to promote better understanding and improved outcomes of patient care.

Target Audience

Interventional radiologists, oncologists, radiation oncologists, transplant and oncologic surgeons, hepatologists, gastroenterologists, urologists and nurse practitioners/nurses, technologists and allied healthcare professionals.

Learning Objectives

At the completion of the course, attendees will be able to: • Identify the current oncological problems faced in a variety of organ systems • Implement modern multidisciplinary techniques for diagnosis and intervention in the treatment of cancer • Incorporate modern interventional radiology therapeutic techniques in cancer treatment • Examine the basics of BPH and the current management guidelines • Assess prostatic arterial vasculature • Identify the current status and challenges with Prostate Artery Embolization in the management of BPH and prostate cancer • Implement modern multidisciplinary techniques for diagnosis and intervention in the management of BPH

Accreditation

The University of Miami Leonard M. Miller School of Medicine is accredited by the ACCME to provide continuing medical education for physicians.

AGENDA

http://synergymiami.org/media/Synergy-2015-Brochure-2015-09-11.pdf

SOURCE

http://synergymiami.org/media/Synergy-2015-Brochure-2015-09-11.pdf

 

 

 

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Cancer Biology and Genomics for Disease Diagnosis (Vol. I) Now Available for Amazon Kindle


Cancer Biology and Genomics for Disease Diagnosis (Vol. I) Now Available for Amazon Kindle

Reporter: Stephen J Williams, PhD

Leaders in Pharmaceutical Business Intelligence would like to announce the First volume of their BioMedical E-Book Series C: e-Books on Cancer & Oncology

Volume One: Cancer Biology and Genomics for Disease Diagnosis

CancerandOncologyseriesCcoverwhich is now available on Amazon Kindle at                          http://www.amazon.com/dp/B013RVYR2K.

This e-Book is a comprehensive review of recent Original Research on Cancer & Genomics including related opportunities for Targeted Therapy written by Experts, Authors, Writers. This ebook highlights some of the recent trends and discoveries in cancer research and cancer treatment, with particular attention how new technological and informatics advancements have ushered in paradigm shifts in how we think about, diagnose, and treat cancer. The results of Original Research are gaining value added for the e-Reader by the Methodology of Curation. The e-Book’s articles have been published on the Open Access Online Scientific Journal, since April 2012.  All new articles on this subject, will continue to be incorporated, as published with periodical updates.

We invite e-Readers to write an Article Reviews on Amazon for this e-Book on Amazon. All forthcoming BioMed e-Book Titles can be viewed at:

https://pharmaceuticalintelligence.com/biomed-e-books/

Leaders in Pharmaceutical Business Intelligence, launched in April 2012 an Open Access Online Scientific Journal is a scientific, medical and business multi expert authoring environment in several domains of  life sciences, pharmaceutical, healthcare & medicine industries. The venture operates as an online scientific intellectual exchange at their website http://pharmaceuticalintelligence.com and for curation and reporting on frontiers in biomedical, biological sciences, healthcare economics, pharmacology, pharmaceuticals & medicine. In addition the venture publishes a Medical E-book Series available on Amazon’s Kindle platform.

Analyzing and sharing the vast and rapidly expanding volume of scientific knowledge has never been so crucial to innovation in the medical field. WE are addressing need of overcoming this scientific information overload by:

  • delivering curation and summary interpretations of latest findings and innovations
  • on an open-access, Web 2.0 platform with future goals of providing primarily concept-driven search in the near future
  • providing a social platform for scientists and clinicians to enter into discussion using social media
  • compiling recent discoveries and issues in yearly-updated Medical E-book Series on Amazon’s mobile Kindle platform

This curation offers better organization and visibility to the critical information useful for the next innovations in academic, clinical, and industrial research by providing these hybrid networks.

Table of Contents for Cancer Biology and Genomics for Disease Diagnosis

Preface

Introduction  The evolution of cancer therapy and cancer research: How we got here?

Part I. Historical Perspective of Cancer Demographics, Etiology, and Progress in Research

Chapter 1:  The Occurrence of Cancer in World Populations

Chapter 2.  Rapid Scientific Advances Changes Our View on How Cancer Forms

Chapter 3:  A Genetic Basis and Genetic Complexity of Cancer Emerge

Chapter 4: How Epigenetic and Metabolic Factors Affect Tumor Growth

Chapter 5: Advances in Breast and Gastrointestinal Cancer Research Supports Hope for Cure

Part II. Advent of Translational Medicine, “omics”, and Personalized Medicine Ushers in New Paradigms in Cancer Treatment and Advances in Drug Development

Chapter 6:  Treatment Strategies

Chapter 7:  Personalized Medicine and Targeted Therapy

Part III.Translational Medicine, Genomics, and New Technologies Converge to Improve Early Detection

Chapter 8:  Diagnosis                                     

Chapter 9:  Detection

Chapter 10:  Biomarkers

Chapter 11:  Imaging In Cancer

Chapter 12: Nanotechnology Imparts New Advances in Cancer Treatment, Detection, &  Imaging                                 

Epilogue by Larry H. Bernstein, MD, FACP: Envisioning New Insights in Cancer Translational Biology

 

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Ablation Techniques in Interventional Oncology

Author and Curator: Dror Nir, PhD

“Ablation is removal of material from the surface of an object by vaporization, chipping, or other erosive processes.”; WikipediA.

The use of ablative techniques in medicine is known for decades. By the late 90s, the ability to manipulate ablation sources and control their application to area of interest improved to a level that triggered their adaptation to cancer treatment. To date, ablation  is still a controversial treatment, yet steadily growing in it’s offerings to very specific cancer patients’ population.

The attractiveness in ablation as a form of cancer treatment is in the promise of minimal invasiveness, focused tissue destruction and better quality of life due to the ability to partially maintain viability of affected organs.  The main challenges preventing wider adaptation of ablative treatments are: the inability to noninvasively assess the level of cancerous tissue destruction during treatment; resulting in metastatic recurrence of the disease and the insufficient isolation of the treatment area from its surrounding.   This frequently results In addition, post-ablation salvage treatments are much more complicated. Since failed ablative treatment represents a lost opportunity to apply effective treatment to the primary tumor the current trend is to apply such treatments to low-grade cancers.

Nevertheless, the attractiveness of treating cancer in a focused way that preserves the long-term quality of life continuously feeds the development efforts and investments related to introduction of new and improved ablative treatments giving the hope that sometime in the future focused ablative treatment will reach its full potential.

The following paper reviews the main ablation techniques that are available for use today: Percutaneous image-guided ablation of bone and soft tissue tumours: a review of available techniques and protective measures.

Abstract

Background

Primary or metastatic osseous and soft tissue lesions can be treated by ablation techniques.

Methods

These techniques are classified into chemical ablation (including ethanol or acetic acid injection) and thermal ablation (including laser, radiofrequency, microwave, cryoablation, radiofrequency ionisation and MR-guided HIFU). Ablation can be performed either alone or in combination with surgical or other percutaneous techniques.

Results

In most cases, ablation provides curative treatment for benign lesions and malignant lesions up to 3 cm. Furthermore, it can be a palliative treatment providing pain reduction and local control of the disease, diminishing the tumor burden and mass effect on organs. Ablation may result in bone weakening; therefore, whenever stabilization is undermined, bone augmentation should follow ablation depending on the lesion size and location.

Conclusion

Thermal ablation of bone and soft tissues demonstrates high success and relatively low complication rates. However, the most common complication is the iatrogenic thermal damage of surrounding sensitive structures. Nervous structures are very sensitive to extremely high and low temperatures with resultant transient or permanent neurological damage. Thermal damage can cause normal bone osteonecrosis in the lesion’s periphery, surrounding muscular atrophy and scarring, and skin burns. Successful thermal ablation requires a sufficient ablation volume and thermal protection of the surrounding vulnerable structures.

Teaching points

Percutaneous ablations constitute a safe and efficacious therapy for treatment of osteoid osteoma.

Ablation techniques can treat painful malignant MSK lesions and provide local tumor control.

Thermal ablation of bone and soft tissues demonstrates high success and low complication rates.

Nerves, cartilage and skin are sensitive to extremely high and low temperatures.

Successful thermal ablation occasionally requires thermal protection of the surrounding structures.

For the purpose of this chapter we picked up three techniques:

Radiofrequency ablation

Straight or expandable percutaneously placed electrodes deliver a high-frequency alternating current, which causes ionic agitation with resultant frictional heat (temperatures of 60–100 ˚C) that produces protein denaturation and coagulation necrosis [8]. Concerning active protective techniques, all kinds of gas dissection can be performed. Hydrodissection is performed with dextrose 5 % (acts as an insulator as opposed to normal saline, which acts as a conductor). All kinds of skin cooling, thermal and neural monitoring can be performed.

 

Microwave ablation

Straight percutaneously placed antennae deliver electromagnetic microwaves (915 or 2,450 MHz) with resultant frictional heat (temperatures of 60–100 ˚C) that produces protein denaturation and coagulation necrosis [8]. Concerning active protective techniques, all kinds of gas dissection can be performed, whilst hydrodissection is usually avoided (MWA is based on agitation of water molecules for energy transmission). All kinds of skin cooling, thermal and neural monitoring can be performed.

Percutaneous ablation of malignant metastatic lesions is performed under imaging guidance, extended local sterility measures and antibiotic prophylaxis. Whenever the ablation zone is expected to extend up to 1 cm close to critical structures (e.g. the nerve root, skin, etc.), all the necessary thermal protection techniques should be applied (Fig. 3).

13244_2014_332_Fig3_HTML

a Painful soft tissue mass infiltrating the left T10 posterior rib. b A microwave antenna is percutaneously inserted inside the mass. Due to the proximity to the skin a sterile glove filled with cold water is placed over the skin. c CT axial scan 3 months

Irreversible Electroporation (IRE)

Each cell membrane point has a local transmembrane voltage that determines a dynamic phenomenon called electroporation (reversible or irreversible) [16]. Electroporation is manifested by specific transmembrane voltage thresholds related to a given pulse duration and shape. Thus, a threshold for an electronic field magnitude is defined and only cells with higher electric field magnitudes than this threshold are electroporated. IRE produces persistent nano-sized membrane pores compromising the viability of cells [16]. On the other hand, collagen and other supporting structures remain unaffected. The IRE generator produces direct current (25–45 A) electric pulses of high voltage (1,500–3,000 V).

Lastly we wish to highlight a method that is mostly used on patients diagnosed at intermediate or advanced clinical stages of Hepatocellular Carcinoma (HCC); transarterial chemoembolization  (TACE)

“Transcatheter arterial chemoembolization (also called transarterial chemoembolization or TACE) is a minimally invasive procedure performed in interventional radiology  to restrict a tumor’s blood supply. Small embolic particles coated with chemotherapeutic agents are injected selectively into an artery directly supplying a tumor. TACE derives its beneficial effect by two primary mechanisms. Most tumors within the liver are supplied by the proper hepatic artery, so arterial embolization preferentially interrupts the tumor’s blood supply and stalls growth until neovascularization. Secondly, focused administration of chemotherapy allows for delivery of a higher dose to the tissue while simultaneously reducing systemic exposure, which is typically the dose limiting factor. This effect is potentiated by the fact that the chemotherapeutic drug is not washed out from the tumor vascular bed by blood flow after embolization. Effectively, this results in a higher concentration of drug to be in contact with the tumor for a longer period of time. Park et al. conceptualized carcinogenesis of HCC as a multistep process involving parenchymal arterialization, sinusoidal capillarization, and development of unpaired arteries (a vital component of tumor angiogenesis). All these events lead to a gradual shift in tumor blood supply from portal to arterial circulation. This concept has been validated using dynamic imaging modalities by various investigators. Sigurdson et al. demonstrated that when an agent was infused via the hepatic artery, intratumoral concentrations were ten times greater compared to when agents were administered through the portal vein. Hence, arterial treatment targets the tumor while normal liver is relatively spared. Embolization induces ischemic necrosis of tumor causing a failure of the transmembrane pump, resulting in a greater absorption of agents by the tumor cells. Tissue concentration of agents within the tumor is greater than 40 times that of the surrounding normal liver.”; WikipediA

A recent open access research paper: Conventional transarterial chemoembolization versus drug-eluting bead transarterial chemoembolization for the treatment of hepatocellular carcinoma is discussing recent clinical approaches  related to this techniques.

Abstract

Background

To compare the overall survival of patients with hepatocellular carcinoma (HCC) who were treated with lipiodol-based conventional transarterial chemoembolization (cTACE) with that of patients treated with drug-eluting bead transarterial chemoembolization (DEB-TACE).

Methods

By an electronic search of our radiology information system, we identified 674 patients that received TACE between November 2002 and July 2013. A total of 520 patients received cTACE, and 154 received DEB-TACE. In total, 424 patients were excluded for the following reasons: tumor type other than HCC (n = 91), liver transplantation after TACE (n = 119), lack of histological grading (n = 58), incomplete laboratory values (n = 15), other reasons (e.g., previous systemic chemotherapy) (n = 114), or were lost to follow-up (n = 27). Therefore, 250 patients were finally included for comparative analysis (n = 174 cTACE; n = 76 DEB-TACE).

Results

There were no significant differences between the two groups regarding sex, overall status (Barcelona Clinic Liver Cancer classification), liver function (Child-Pugh), portal invasion, tumor load, or tumor grading (all p > 0.05). The mean number of treatment sessions was 4 ± 3.1 in the cTACE group versus 2.9 ± 1.8 in the DEB-TACE group (p = 0.01). Median survival was 409 days (95 % CI: 321–488 days) in the cTACE group, compared with 369 days (95 % CI: 310–589 days) in the DEB-TACE group (p = 0.76). In the subgroup of Child A patients, the survival was 602 days (484–792 days) for cTACE versus 627 days (364–788 days) for DEB-TACE (p = 0.39). In Child B/C patients, the survival was considerably lower: 223 days (165–315 days) for cTACE versus 226 days (114–335 days) for DEB-TACE (p = 0.53).

Conclusion

The present study showed no significant difference in overall survival between cTACE and DEB-TACE in patients with HCC. However, the significantly lower number of treatments needed in the DEB-TACE group makes it a more appealing treatment option than cTACE for appropriately selected patients with unresectable HCC.

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