Advances in Interventional Radiology That Patients and Survivors Need to Know

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Advances in Interventional Radiology That Patients and Survivors Need to Know Cancer Treatment Centers of America Western Regional Medical Center Goodyear, AZ Presented by: Aaron Wittenberg, MD Interventional Radiology Liver Directed Therapies: Yttrium 90 Treatment Radiofrequency Ablation

What is Interventional Radiology Many people do not know Specialize in a broad range of minimally invasive, targeted procedures Less pain and recovery time compared to conventional treatments Use x-rays to advance a catheter or other device to treat a disease internally Rely on our background as experts in medical imaging

309-M-PPP US rev. 0 The concept of Y90 To selectively target a radiation dose high enough to kill tumors cells within the liver, while at the same time Maintaining a low radiation dose to the normal liver

Yttrium-90 Microspheres Delivery of millions of tiny radioactive beads directly to liver tumors The beads are tiny approximately 1/3 the diameter of a strand of hair They lodge in the smallest arteries supplying the tumor in order to destroy them

Y90 is a minimally invasive therapy in which a trans-femoral microcatheter is used to gain access to the hepatic artery supplying the liver 309-M-PPP US rev. 0

How Y90 Works Radiation is an effective way to destroy tumor tissues and is used widely in cancer treatment However, the organs and tissues in the body are sensitive to radiation and may also be damaged by radiation treatment. Conventional radiotherapy (external beam radiation delivered from outside the body) can only be given to limited areas of the body. The liver can only tolerate small doses of external radiotherapy. Selective Internal Radiation Therapy (SIRT) with Y90 microspheres targets the tumors internally, it can deliver a larger dose of radiation directly over a longer time than is possible with external beam radiation. This allows therapeutic radiation to be targeted within the liver tumors. Although normal liver tissue will be radiated to some extent, the radiation dose is well below the limit the tissue can tolerate without serious damage.

How do the spheres get to the tumor? Liver Tumors get most of their blood supply from the hepatic artery, the main artery that supplies blood to the liver. Normal liver tissue gets most of its blood supply from a blood vessel called the portal vein. Microspheres are injected into the hepatic artery so they are mainly delivered to the tumor.

How Y90 Works The microspheres become trapped in the very small blood vessels of the tumor where they deliver their radiation dose to an area of about 2-3mm (about 1/8 ) around where they are trapped. Most of the radiation is delivered within 2 weeks. In this way, radiation is delivered mostly to the tumor but causes very little damage to the surrounding healthy liver tissue.

Hepatic Artery Radiation Therapy Microsphere radiation therapy exploits the anatomical and physiological characteristics of vasculature and tolerance Tumor vessels 25μm -75μm diameter End arterioles 8μm diameter SIR-Spheres mean diameter 32.5μm

Relative Sizes in microns Object Size in microns Size in inches Wood smoke particles < 1 micron 0.00004 Bacteria 2 0.00008 RBC 8 0.0003 WBC 25 0.001 Y90 particle 35 0.0015 Human Hair 75 0.003 Grain of salt 100 0.004

Entrapment of SIR-Spheres in vascular Bed

Increased Flow

Radiation Emitted Y90 patient at 12 inches =3 mrem/hr for first 5-6 hours CXR= 8 mrem Airplane 1mrem/hr CT abdomen= 1200 mrem Normal background in US 300-350 mrem/year Chernnobyl 100,000mRem. 10,000mrem at 15 mi

Side effects Side effects of Selective Internal Radiation Therapy (SIRT) are usually mild. You may have pain in your abdomen or nausea for 1-2 days. You also may have a raised temperature, chills or a feeling of pressure in the abdomen. These side effects are usually gone in a few days. Tiredness and appetite loss are the most common side effects and can last for up to 6 weeks. You may be given medication for a month after treatment to reduce gastritis (stomach upset) and peptic ulceration (stomach ulcers).

Side Effects Delivery of microspheres to other gastrointestinal structures such as the stomach, small intestine, pancreas or other organs can cause ulceration and inflammation which can be troublesome and difficult to treat. If normal liver tissue receives too high a dose of radiation, the normal liver may be severely or even fatally damaged. This is called radiation hepatitis. If too many microspheres pass to the lungs they can cause serious damage (radiation pneumonitis). You will be treated by a doctor who is specially trained to deliver SIRT and to minimize the risk of these things happening. However the risk cannot be eliminated.

Proportion surviving Phase II RCT of SIR-Spheres microspheres + 5- FU/LV first-line chemotherapy vs. 5-FU/LV alone SIR-Spheres + 5-FU/LV in mcrc: Overall Survival 2 1 5-FU/LV Median (months) 12.8 months 0.8 5-FU/LV + SIR-Spheres 29.4 months P =0.025 0.6 0.4 0.2 0 0 6 12 18 24 30 36 Months from randomization significantly longer median overall survival significantly longer median TTP significantly greater response rate quality of life of patients was not compromised

Patient with colon carcinoma after treatment with Y90 and Chemotherapy SIR-Spheres + 5-FU/LV in mcrc: CT Responses 2 CT scan Pre-SIRT CT scan 10 months post-sirt

Patient with colon carcinoma, after treatment with Y90 and FOLFOX SIR-Spheres + FOLFOX4 in mcrc: CT Responses 4 Baseline CT scan pre-sirt CT scan 6 months post-sirt Patient was subsequently resected

Colorectal liver metastases: before and response 15 months after treatment with SIR-Spheres + 5FU/LV

RFA--Introduction What is RFA? Directed RF energy causes frictional heating of tissues Cell death occurs at 60 degrees C Uses include liver tumors, renal tumors, lung tumors, bone/soft tissue Can be used as stand alone treatment or in conjunction with chemotherapy/radiation therapy

Procedure Overview A radiofrequency electrode is inserted under image guidance (Ultrasound / CT) An umbrella-shaped array is deployed in the tumor The electrode is connected to an RF generator The targeted tissue heated to induce cellular destruction Power is applied until tissue impedance (resistance to electrical current) rises Generator detects impedance rise and signals completion of procedure

RFA Generator Needle-electrode is inserted into lesion with image guidance The patient is turned into an electrical circuit by placing grounding pads on the back of their thighs

Application of Radiofrequency Energy LeVeen TM Electrode RF3000 TM Generator Patient return pads (4 total; 2 on each thigh)

CT Evaluation (1) Colorectal metastatic tumor (approx. 3x3 cm) (2) 6 months post procedure (approx. 5x4.5 cm due to targeted margin) 1 Year Follow-Up * No new metastatic tumors were present at the point of RF ablation in the right lobe, and no new metastatic tumors were present in other regions of the liver. (3) 12 months post procedure (approx. 2 x 2 cm)

CT Guided Soft Tissue RFA of met lesion Lesion #1 Lesion #2

The End. Thanks for your time!