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Running Header: CASE STUDY OF RECURRENT Case Study of Recurrent T2a N0 Prostate Cancer Rob Cox-Vari Argosy University- Twin Cities 1 CASE STUDY OF RECURRENT Case Study of Recurrent T2a N0 Prostate Cancer The patient chosen for the case study was a 64 year old male, who for the purposes of confidentiality will be called Joe. Joe came to the clinic with recurrent T2aN0 adenocarcinoma of the prostate, meaning that the tumor had originally involved one-half of one lobe or less with no local nodal involvement, and the tumor had returned. This case study documents the patient’s journey from the initial consultation through the follow-up appointment one month after completion of treatment, including prostate cancer natural history and other available treatment options. In July 2012 that patient was originally seen for elevated PSA, leading to a transrectal ultrasound biopsy that showed adenocarcinoma, for which a radical retropubic prostatectomy was performed in September 2012 with no concurrent radiation; however, included a regiment of hormone therapy. A PET scan done 4 months later showed a possible right scapula lesion, but the biopsy of the lesion was negative. Since the patient was experiencing pain in that region and the radiation oncologist believed the region to be pre-cancerous, radiation treatment to the area was given, involving 10 fractions with a total dose of 3000cGy. A follow-up appointment was conducted in December 2013, where the Joe noted increased nocturia, or waking up in the night repeatedly to urinate, and blood testing revealed increased PSA of 4.0. A rectal exam, a procedure involving placing two lubricated fingers into the rectum, was performed, noting a palpable mass with no blood in the sphincter. After the Rectal exam was performed a CT was conducted along with a biopsy of the prostate bed and seminal vesicle. The biopsies came back positive for adenocarcinoma and a Gleason score of 8 was assigned by the pathologist. 2 CASE STUDY OF RECURRENT The patient had no family history of cancer, does not smoke, only drinks occasional wine, is on a vegan diet and regularly exercises. The patient does have hypothyroidism, hyperlipidemia, GERD, sinus problems including a deviated septum, and had a basal cell cancer removed on his left upper forehead by Moh’s surgery. The medications the patient was on at the time of initial counsel included levothyroxine, simvastatin, Casodex and Trelstar. After consulting with the patient, and considering the patient’s medical history, a plan for treatment was developed. The patient was to continue the hormone therapy involving two drugs, Casodex, an anti-androgen blocking the effects of testosterone in the body and Trelstar, a medication that suppresses the body’s production of testosterone. Along with hormone therapy, external beam radiation was utilized in the form of IMRT, requiring simulation and planning. The first simulation was used to set the position of the patient. The patient was laying supine with his head resting on a sponge pillow to support the head. His arms were placed on his chest, where he held an O-ring for comfort and to keep the hands and elbows out of the treatment fields. A vac-lock was then placed under the patient’s legs and air was removed from the device to make a mold that would be important in reproducing the same position daily for treatment. Once in position with the vac-lock in place, lasers were used to place temporary markers and BB’s on the two greater trochanters for the lateral marks, and on the symphysis pubis for the AP mark. Once the marks were placed, the CT scanner was ‘zeroed’ and the patient was moved 500cm in to the tube. An initial x-ray was utilized to check the field to be scanned and then the CT was conducted that was then sent to dosimetry for planning. The patient was guided out the CT machine and photographs were taken for the patient’s record. 3 CASE STUDY OF RECURRENT Planning the treatment began with contouring of the internal anatomy seen on the CT in the simulation room, including small bowel, rectum, bladder, and femoral heads. The contouring of the internal organs allows the planning program to keep track of dose to critical structures so that the most sensitive organs can be avoided. Once the doctor drew on the GTV and PTV into the CT, the maximum dosage parameters to the critical structures as well as dosage to the GTV and PTV were inputted into the IMRT planning program. After about an hour of the program optimizing, a plan was presented to the doctor for approval. The dose to the tumor was to be 7400 cGy, with 200 cGy to be delivered daily for 37 fractions at energy of 6MV, through the utilization of 9 field IMRT with dynamic MLC. The 9 angles of treatment are PA, RPO-315, RPO-280, RAO-250, RAO-220, LAO-140, LAO-110, LPO-80 and LPO-45. The plan was approved by the doctor and the patient was called to setup the second simulation. The second simulation occurs in the treatment room, and is called the “dry run”, meaning no treatment; rather images are taken to verify patient position. The patient was positioned on the treatment table in the same position as the initial CT simulation and two kV images were taken to confirm proper patient alignment based on bony anatomy. After remarking the patient and confirming the SSD’s, the patient was given permanent tattoos, two laterals and one AP, for ease of preserving marks for positioning. Daily treatment was completed on a Varian Clinac brand machine with the patient placed in the vac-lock and positioned by aligning the 3 tattoos the patient received on the first day. Once in position and the SSD checked, the OBI or on-board imaging arms were lowered and CBCT or cone beam CT taken to localize the tumor and prostate bed. Once localized, the treatment began, monitor units were checked at each angle and the treatment was conducted, with the gantry manually being moved from angle to angle and the MLC dynamically moving 4 CASE STUDY OF RECURRENT while the beam was on. The system used was Mosaiq, so all of the information from treatment automatically got recorded daily, including MU’s, total dose received daily and cumulative dose. Every five days the SSD’s of the lateral and AP were taken to ensure no significant weight loss or change in body habitus. Over the entire course of the treatment the patient is seen weekly by the doctor to monitor any changes in patient due to radiation. During the first three weeks, Joe experienced no side effects or symptoms. Through weeks 4 and 5 the patient experienced mild urinary symptoms that were treated with cranberry juice, and mild diarrhea which was treated with Imodium. Week 6 saw no new side effects or symptoms and by week 7 the patient was experiencing an increase in diarrhea that was treated by increasing the Imodium. The main symptom concerning the doctor, fatigue, never materialized, most likely as a result of the patient’s active lifestyle. One month after completion of treatment, the patient returned to have his follow-up appointment. The patient did not experience any lingering side effects such as organmegaly from treatment. The patient was instructed to continue with his hormone therapy of Casodex and Treslstar. The prostate is a male reproductive gland responsible for producing the alkaline fluid part of the seminal fluid ejected during sexual intercourse. The prostate is located anterior the rectum and inferior the bladder, surrounding the prosthetic urethra which is a tube that extends from the inferior bladder to the tip of the penis and is the tube that drains fluid from the bladder and semen out the penis (Kelley, 2013). The most common type of prostate cancer is adenocarcinoma, developing most commonly in the peripheral glands and having the potential to invade surrounding tissue such as 5 CASE STUDY OF RECURRENT the seminal vesicles, rectum or bladder. If left untreated prostate cancer has the potential to metastasize to the regional lymph nodes; periprostatic and obturator nodes first then the external iliac, hypogastric, common iliac and periaortic nodes then to bone located throughout the body (Washington, 2010). Prostate cancer is the number one malignancy in males in the United States, with 1 in 6 men developing the cancer and accounting for 65% of cancers in males ages 65 and older (Washington, 2010). It is estimated that in the year 2014 that there will 233,000 new cases of prostate cancer, and account for 29,480 deaths (National Cancer Institute, 2014). According to the American Cancer Society, 1 in 36 men will die from prostate cancer, second behind lung cancer; however, the majority of males diagnosed with prostate cancer will not die, as there are 2.5 million men that have been diagnosed that are alive. The relative 5-year survival rate is about 100% with the 10-year rate at almost 99% and the 15-year survival rate is 94%, for all stages of cancer (American Cancer Society, 2014). The cause of prostate cancer is unknown, but there are factors that have been correlated with higher rates of incidence. The first risk factor is age, with only about 1 in 10,000 under the age of 40 being diagnosed, but the rate jumps dramatically when compared to the age group of men ages 60 to 69, where the ratio goes to 1 in 14 (Prostate Cancer Foundation, 2014). Another factor that can increase the risk of prostate cancer is family history. If a family member has prostate cancer or there is a history of breast cancer, including BRCA1 and BRCA2 positive, the individual is at higher risk of being diagnosed with prostate cancer. (Mayo Clinic, 2014). Race can also be a major risk factor, as African Americans have a higher incidence rate and are 2.5 times more likely to die from the disease (Prostate Cancer Foundation, 2014). According to the US National Library of Medicine, other risk factors include being exposed to Agent Orange, 6 CASE STUDY OF RECURRENT having a high fat diet, drinking excessive amounts of alcohol, working at a tire plant, painting for a living, being a farmer, and cadmium exposure can increase the chances of getting prostate cancer, but being a vegetarian can decrease the risk. There are multiple methods utilized to detect, diagnose and stage prostate cancer. The two most common means in detecting the presence of prostate cancer are a DRE or digital rectal exam and a PSA or prostate-specific antigen blood test. The digital rectal exam is performed by a physician wearing gloves, lubricating two fingers and inserting them into the rectum to feel for any bumps or swelling of the prostate gland. A PSA blood test performed looking for prostate-specific antigen that is found in low levels in blood, about 4 nanograms per milliliter of blood, as having prostate cancer should increase these levels in the blood (American Cancer Society, 2014). When a test comes back with an elevated PSA or a mass is palpated during a DRE, a transrectal ultrasound guided biopsy is performed. The core of the biopsy is then sent to a pathologist who evaluates the morphology and differentiation of the sample, giving them both a score of 1 to 5 with both those scores added together to give the Gleason score which is closely tied to prognosis (Washington, 2010). Other modalities for diagnosing and staging of prostate cancer include the use of MRI, CT, and PET scans if it is believed to have metastasized to other parts of the body. In the event that a positive diagnosis is confirmed, a number of treatment options that are available to patients with this disease outside the most common approaches of watchful waiting, radical prostatectomy, hormonal therapy and external beam radiation. Another option available to patients is internal radiation or brachytherapy, coming in two forms LDR, low-dose rate, and HDR, high-dose rate. 7 CASE STUDY OF RECURRENT For the LDR setup, a patient is placed in the dorsal lithotomy position, where they are on their back with their legs above their heads typically in stirrups for support. A template or grid is pressed against the perineum, the region between the male anus and scrotum, and transrectal sonography is used to guide about 25 needles into the prostate, where about 100 seeds are permanently deposited about 1 cm apart. The most commonly used isotopes for treatment are I125, iodine, with a half-life of 60 days, and Pd-103, palladium, with a half-life of 17 days. The typical dose delivered for treatment by iodine is 145Gy and the dose for palladium is 115Gy. The planning is accomplished with the patient in the treatment room prior to insertion of the needles with the use of ultra sound images and then verified after seeds are inserted by taking CT images of seed placement which are recalculated to verify dose to the prostate. The seeds are permanently implanted into the region and the dose is delivered slowly over time over the course of many days or months (Washington, 2010). HDR brachytherapy places the patient in the same position, dorsal lithotomy, and places the template or grid against the perineum just like LDR. Rather than implanting permanent seeds into the prostate, HDR utilizes the hollow tubes or catheters placed into the prostate via the use of transrectal ultrasound for guidance. Once the tubes are placed within the region to be treated, a CT scan is done to verify tube placement and measure length of catheter into the prostate. The images are sent to dosimetry for planning, where the critical organs are contoured, rectum, small bowel and bladder, and the dose is planned. An after loading device is used to guide the radioactive source, usually Ir-192 or iridium 192, through the catheter into the prostate stopping at certain locations based on planning and dose distribution required. This is an ‘in-patient’ procedure requiring the patient to be hospitalized for 2 days because they are not allowed to 8 CASE STUDY OF RECURRENT move or it would change dose to the organs and desired area. Typical dose to tumor bed is 3600 to 4000 cGy given over two days with treatments twice a day (Mondalek, 2008). Another option available for treatment of prostate cancer is called cryosurgery or cryotherapy, which involves freezing the tumor. The patient is given epidural anesthesia or general anesthesia, and much like HDR brachytherapy hollow tubes are placed into the prostate, using transrectal ultrasound for guidance. Once the tubes are placed, warm saltwater is circulated through the urethra to prevent it from freezing, and cold gas is passed through the tubes creating ‘ice balls’ that destroy the prostate. Once the procedure is completed, the catheter placed is left in the urethra for about 3 weeks to allow emptying of the bladder during recovery. (American cancer Society, 2014) One last form of treatment to discuss available to prostate cancer patients is called highintensity focused ultrasound, which is still in the experimental stages in the US but common practice in the UK. It works in the opposite manner as cryosurgery, in that as cryosurgery cause death to the tissue by freezing, high-intensity focused ultrasound heats the tissue to death. The patient is placed under general anesthesia and then the probe is inserted into the rectum where very high intensity ultrasound waves are aimed and delivered at the target. The ultrasound waves vibrate and heat up the prostate cells killing them. The treatment can take up to 3 hours to complete (Prostate Cancer UK, 2014). Due to the patient’s medical history, and options available for treatment, the dual modalities utilized were the best options for the patient. Brachytherapy of the prostate is best when the prostate is present in the patient, and since Joe had his prostate removed, any seeds or catheters have to chance to migrate around the prostate bed altering the dosage to tumor volume. 9 CASE STUDY OF RECURRENT Cryotherapy would not be an option since the patient already had his prostate and works best when the tumor is present in the prostate. High-intensity focused ultrasound is still in the experimental stage here in the United States, though is a common method in the United Kingdom, so in order to get easy access to the treatment a trip to England would be necessary. Plus cryosurgery and HIFU is often used as an alternative when radiation is not effective at destroying the cancer. So as a result of previous prostatectomy, external radiation utilizing IMRT combined with hormonal therapy was the best option for the patient to get the best results. 10 CASE STUDY OF RECURRENT 11 References American Cancer Society. (2014). Can prostate cancer be found early? at http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-cancer-detection retrieved 5/24/2014 American Cancer Society. (2014). Cryosurgery for prostate cancer at http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-cancer-treating-cryosurgery retrieved on 5/24/2014 American Cancer Society. (2014). Survival rates for prostate cancer at http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-cancer-survival-rates retrieved 5/24/2014 Kelley, L.L. & Petersen, C.M. (2013). Sectional Anatomy for Imaging Professionals. St. Louis, Missouri: Mosby-Elsevier Mayoclinic. (2014). Diseases and Conditions- Prostate Cancer at http://mayoclinic.org/diseases-conditions/prostate-cancer/basics/causes/con-20021597 retrieved on 5/23/2014 Mondalek, P.M. (2010). Review of Prostate Brachytherapy: LDR and HDR at http://www.medicaldosimetry.org/pub/397b5a7d-2354-d714-516a-27fb07acdedd retrieved on 5/25/2014 National Cancer Institue. (2014). Prostate Cancer at http://cancer.gov/cancertopics/types/prostate retrieved on 5/23/2014 CASE STUDY OF RECURRENT Prostate Cancer Foundation. (2014). Prostate Cancer Risk Factors at http://www.pcf.org/site/c.leJRIROrEpH/b.5802027/k.D271/Prostate_Cancer_Risk_Factors.htm retrieved on 5/23/2014 Prostate Cancer UK. (2014). High-Intensity Focused Ultrasound at http://prostatecanceruk.org/information/prostate-cancer/treatment/treatment-choices/hifu retrieved on 5/24/2014 U.S. National Library of Medicine. (2014). Prostate Cancer at http://ncbi.nlm.nih.gov/pubhealth/PMH00148/ retrieved on 5/23/2014 Washington, C.M. & Leaver, D. (2010). Principles and Practice of Radiation Therapy. St. Loius, Missouri: Mosby-Elsevier. 12