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Penile cancer treatment planning technique with matching photonelectron beams: A case study
Amanuel Negussie, B.S. R.T.(T), Nishele Lenards, M.S., CMD, R.T.(R)(T), FAAMD, Joseph G. Lynch, CMD, R.T.(T)(MR), and James Schmitz, A.A.S., CMD, R.T.(T) *Medical Dosimetry Program at the University of Wisconsin - La Crosse, WI and Department of Radiation Oncology, Minneapolis VA Health Care System, Minneapolis, MN Abstract: Introduction: This case study aims to communicate a treatment planning technique to treat penile cancer with matching photon-electron beams. Case Description: A patient with a squamous cell carcinoma of the penis was treated using 45 Gy at 1.8 Gy per fraction to the penis, pelvic and bilateral inguinal nodes with a concurrent electron beam of 45 Gy at 1.8 Gy per fraction to the bilateral inguinal nodes. This was followed by an electron boost to the penile shaft and left inguinal surgical scar. The penile shaft boost was delivered using 20 Gy at 2 Gy per fraction to the penile shaft and the left inguinal scar boost was delivered using 14.4 Gy in 1.8 Gy per fraction. The initial treatment was delivered with parallelopposed photon beams and matching bilateral electron beams. A bolus was used in the anterior aspect of the penis to provide an adequate dose distribution to the target. The boost treatment was delivered with two enface electron fields at 100 SSD. A layer of bolus and lead was used underneath the penis to reduce electron backscatter. Conclusions: Each plan was carefully evaluated based on the dose volume histogram, 100% of the prescription dose coverage, maximum and mean dose to the targets. The skin dose for both initial and boost plans were verified with TLDs. Key words: penile cancer, photon-electron matching, radiation therapy, electron backscatter

2 Introduction Penile cancer is rare and more common in men over age 60.1 It accounts for 1% of cancer in men in the United States and up to 10% in parts of Asia, Africa, and South America.2 The American Cancer Society estimates in the year 2013, there will be about 1,570 new diagnoses and 310 deaths from this cancer.2 Surgery is the most common and effective treatment option for all stages of penile cancer. Radiation therapy can be used as an initial treatment for early stage tumors and as a palliative treatment for advanced cancers.3 It can also be used along with surgery to treat lymph nodes and to reduce a chance of recurrence.3 In younger patients, radiation therapy can be a particularly beneficial alternative treatment as it prevents trauma associated with surgery.1 Radiation therapy is not well utilized in penile cancer treatment, partially due to referral bias.4 External beam radiation therapy (EBRT) and brachytherapy are an effective treatment option for penile cancer patients who seek penile preservation. Brachytherapy has the advantage to deliver higher tumor dose in a shorter time, which can limit tumor repopulation.5 EBRT can be used alone or with surgery, mainly for patients with stage T1N0.4 In a retrospective study from the United Kingdom6, patients with T1N0 penile cancer had a 71% 5 year survival and a 63% recurrence free survival for all stages after EBRT. In addition, Sarin et al7 showed that patients receiving radiation therapy had a significantly higher overall sexual function than those who underwent surgical procedures.7 Case Report A 72-year-old uncircumcised gentleman first noted a penile lesion in 2011. The patient neglected to seek medical attention, as it was painless and looked like a wart. However, he saw a dermatologist as it subsequently began to grow quickly. The patient underwent a shave biopsy in

3 March 2012. The biopsy showed a squamous cell carcinoma that was well differentiated and keratinizing. Given this finding, the patient was seen by a urologist. On examination, a 1.3 cm polypoid mass was noted on the dorsum of the prepuce. Retraction of the prepuce demonstrated numerous other squamous lesions along with hyperemic changes of the glans. Inguinal examination revealed bilateral palpable inguinal adenopathy. A penis glans biopsy showed linchenoid inflammatory infiltrate with mild epidermal atypia. It also demonstrated a larger polypoid lesion with infiltrating and well-differentiated squamous cell carcinoma that extended to the subepithelial connective tissue. The lesion measured 7 mm in thickness. There was also a secondary lesion that showed squamous cell carcinoma in situ with focal invasion. In addition, a diagnostic CT scan showed a mildly enlarged left external iliac node measuring 1.6 x 1.0 cm. The disease was staged rT1aN1M0 squamous carcinoma of the penis. The treatment options available for penile cancer were discussed with the patient. The patient declined to undergo surgery and chose to proceed with radiation therapy. Given the size of his hernia and its proximity to the penis, it was recommended that he undergo a repair procedure. It was also recommended that he have a circumcision procedure before starting his treatment. In penile cancer patients, circumcision prior to beginning a radiation treatment minimizes swelling, skin irritation, moist desquamation, and secondary infection.8 The patient underwent both procedures as recommended. Prescription Prescription for the initial treatment to the penis, pelvis, and inguinal nodes was 45 Gy at 180 cGy per fraction. A concurrent dose of 22.5 Gy at 90 cGy per fraction was prescribed to the bilateral inguinal nodes using electron beams. The boost was prescribed to 20 Gy at 200 cGy per fraction to the penile shaft and 14.4 Gy at 180 cGy per fraction to the left inguinal scar.

4 Simulation The patient was placed supine on the computed tomography (CT) simulator couch in a frog-leg position to avoid skin fold in the pubic region and minimize complication. A Vac-Lok cushion was used to form a custom mold of the patients setup position. The radiation oncologist marked the surgical scar with a solder wire. Two pieces of styrofoam were placed under the scrotum for support and immobilization. A 1 cm pink bolus was molded into shape to fit over the penis. In addition, a 1 cm bolus was placed on top of the surgical scar. The treatment planning CT (TPCT) was taken with 3 mm slices from the second lumbar spine (L2) to mid femur. The radiation oncologist placed the isocenter. Various techniques can be used to immobilize the penis, including Perspex block and water bath.9 It is essential to utilize devices that can be maintained as the penis possibly swells during the treatment course. Target Delineation The TPCT scan was imported into Pinnacle3 9.0 treatment planning system (TPS). The medical dosimetrist contoured all the organs at risk (OR) including rectum, right and left femur, and bladder along with the solder wire. The radiation oncologist contoured the surgical drainage sites, shaft of the penis, external genitalia, and the pelvic vessels to define the treatment volume. The pelvic vessels were used as a substitute for corresponding pelvic lymph nodes as this technique is widely used. The anterior (AP) and posterior (PA) treatment fields were designed using the contoured structures. No definite margin was used. The fields were systematically constructed to include the targets. The AP field included the penis, pelvic and bilateral inguinal lymph nodes (Fig. 1). The left field edge was extended to cover the positive nodal margin (Fig. 1). The posterior (PA) field was narrower and only incorporated the penis and pelvic nodes (Fig. 1). This

5 was done purposely to decrease toxicity to the femoral heads. In addition, the inferior field border was set lower to cover the drainage sites. Treatment Planning - Initial The photon field was designed using 6 MV for the AP field and 18 MV for the PA field. The TPS was set to deliver a point dose of 45 Gy to the isocenter equally weighted from both angles. After careful revision, the weighting was adjusted to achieve better dose coverage to the target. An 18 MV field in field photon beam was also created from the AP field to minimize the hot spot located in the genitalia area. It was not possible to use a hard wedge because of the field size. The right and left anterior inguinal electron fields were planned using 16 MeV electron beams (Fig. 2). The medial border was matched with the PA photon beams lateral border (Fig. 3). The electron fields were constructed in the TPS by the radiation oncologist. The calculation points were placed at 2.8 cm depth. The TPS was set to deliver a point dose of 22.5 Gy at dmax for each electron field. The plan was optimized and reviewed carefully to ensure adequate target coverage. While assessing the composite photon and electron plans, the skin dose was higher on the left inguinal region. As a result, the bolus placed on top of the surgical scar was removed to minimize the dose to that region. This was accomplished by contouring the bolus and assigning it with a density equivalent to air. The weighting of the photon beams were adjusted accordingly to achieve better target coverage (Fig. 4 and Fig. 5). The plan was completed with a total maximum dose of 65 Gy located at the edge of the genitalia. A monitor unit check was performed with MuCheck 8.2.0. The plan was approved with mu difference less than 3%. During treatment, the electron fields were matched with the PA photon beam by shifting laterally from the isocenter. A daily KV image was taken to verify the patient position. The scrotum was

6 also protected by taping it away from the treatment fields. In addition, the dose to skin was verified using thermoluminescent dosimeters (TLDs). The result showed the treatment dose was delivered appropriately as planned. Treatment Planning - Boost The left inguinal surgical scar and the penile shaft received a radiation dose boost with an electron beam. A clinical setup was used to determine the treatment area, the gantry angle, the collimator angle, and the couch angle. The patient was positioned the same as the initial treatment. The anterior portion of the penis was wrapped with a customized 1 cm bolus. The posterior aspect of the penis was supported in a layer of 1 cm bolus, 4.5 mm lead, and a styrofoam (Fig. 6). A layer of bolus and lead are clinically proven to be efficient in dissipating backscattered electrons. Thickness of the absorber materials required to minimize the electron backscatter can be mathematically determined.10 The left inguinal boost was prescribed to 16 MeV at 90% for 180 cGy per fraction to a total dose of 14.4 Gy and a cumulative dose of 59.4 Gy. This was delivered with a 15 x 15 cm cone size and a custom cutout block at 100 SSD (Fig. 7). The penile shaft boost was prescribed to 9 MeV at 90% for 200 cGy per fraction to a total dose of 20 Gy and a cumulative dose of 65 Gy. This was delivered using a 6 x 6 cm open field cone size at 100 SSD (Fig. 7). Since the boost field is a clinical setup, the radiation oncologist determined a composite plan would not be beneficial. The skin dose of both boost fields was verified with TLDs. During the initial treatment, the patient experienced acute scrotal swelling. An ultrasound study demonstrated diffused edema. Therefore, the patient was placed on hold for one week after the 22nd fraction. The patient was treated with Keflex (7 day course) and Fluconazole (1 day course). The treatment was resumed with no other complications.

7 Conclusion Due to the rarity of treating penile cancer with external beam radiation, it is important to work as a team to ensure accuracy and minimize side effects. Immobilization devices should be carefully determined to ensure accuracy and reproducibility. Matching photon-electron beams can provide a homogenous dose distribution to the penis and regional lymph nodes. However, the beam arrangements and blockings should be strategically arranged to minimize an overlap between the posterior photon and the bilateral inguinal electron beams. In addition, a skin dose should be carefully examined near the photon-electron match region.

8 References 1. Turner B, Drudge-Coates L, Henderson S. Nursing Standard. 2013;27(29):50-57. 2. American Cancer Society. What are the key statistics about penile cancer? http://www.cancer.org/cancer/penilecancer/detailedguide/penile-cancer-key-statistics. Accessed June 25, 2013. 3. American Cancer Society. Radiation Therapy for Penile Cancer. http://www.cancer.org/cancer/penilecancer/detailedguide/penile-cancer-treating-radiationtherapy. Accessed July 4, 2013. 4. Burt LM, Shrieve DC, Tward JD. Stage presentation, care patterns, and treatment outcomes for squamous cell carcinoma of the penis. Int J Radiat Oncol Biol Phys. 2013. In Press. doi:10.1016/j.ijrobp.2013.08.013 5. de Crevoisier RD, Slimane K, Sanfilippo N, et al. Long-term results of brachytherapy for carcinoma of the penis confined to the glans (N- or NX). Int J Radiat Oncol Biol Phys. 2009;74(4):1150-1156. doi:10.1016/j.ijrobp.2008.09.054 6. Mistry T, Jones RW, Dannatt E, et al. A 10-year retrospective audit of penile cancer management in the UK. BJU Int. 2007;100(6):1277-1281. doi:10.1111/j.1464410X.2007.07168.x 7. Sarin R, Norman AR, Steel GG, et al. Treatment results and prognostic factors in 101 men treated for squamous carcinoma of the penis. Int J Radiat Oncol Biol Phys. 1997;38(4):713722. 8. Chao K.S C, Perez CA, Brady LW. Radiation Oncology Management Decisions. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2011.

9 9. Crook J, Ma C, Grimard L. Radiation therapy in the management of the primary penile tumor: an update. World J Urol. 2009;27(2):189-196. doi:10.1007/s00345-008-0309-5 10. Khan FM. The Physics of Radiation Therapy. 4th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2010.

10 Figures

Fig. 1. Beams eye view of the anterior and posterior photon fields. The green contoured structure represents the pelvic vessels, the red line represents the patients surgical scar, the red oval shaped structure represents the penile shaft, the orange contoured structure represents the genitalia, and the two small green circles represent the surgical drainage sites.

Fig. 2. Beams eye view (BEV) of the bilateral electron fields

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Fig. 3. Field matching of the bilateral anterior electron beams with a posterior photon field

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Fig. 4. The sagittal, axial, and coronal views of dose distribution. The red isodose line represents 45 Gy and yellow isodose line represents 22.5 Gy.

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Fig. 5. Dose volume histogram (DVH) of the initial plan demonstrating dose distribution to the penile shaft, pelvic vessels, and OR.

Fig. 6. A layer of bolus and lead placed underneath the penis to reduce electron backscatter

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Fig. 7. Monitor unit calculation for the left inguinal and penile shaft boost fields