The Brachytherapy “Bermuda Triangle”: A Potential Space with Important Implications for LDR and HDR Prostate Brachytherapy

Abstracts / Brachytherapy 15 (2016) S21eS204 PO167 Needle Migration in High Dose Rate Brachytherapy for Prostate Cancer Evaluated by Serial MRI and Photos Simon Buus, MD, PhD1, Steffen Bjerre Hokland, PhD2, Susanne Rylander, MSc2, Erik Morre Pedersen, DMSc, PhD3, Lise Bentzen, MD, PhD1, Kari Tanderup, PhD2. 1Dept. of Oncology, Aarhus University Hospital, Aarhus, Denmark; 2Dept. of Medical Physics, Aarhus University Hospital, Aarhus, Denmark; 3Dept. of Radiology, Aarhus University Hospital, Aarhus, Denmark. Purpose: Needle migration may be a concern in MRI based high dose rate brachytherapy (HDR-BT) for prostate cancer due to an increased time consumption when compared with ultrasound based HDR-BT. Movement of the needles in relation to the prostate may lead to insufficient target coverage and an increased dose to organs at risk. The aim of this study was to assess the magnitude of needle migration in HDR-BT with serial MRI and photos. Materials and Methods: 5 patients with high risk prostate cancer treated with EBRT and two boosts of HDR-BT were included in the study. In order to fixate the needles, a thin silicone pad was placed within the template, which was fixated to perineum with 4 sutures. The position of the template was marked with indian ink on the thighs of patients, and photos of the perineum (Fig. 1) were taken before and after each MRI. Following the ultrasound guided needle implant, the patient was placed in supine position on a MRI couch on a trolley, where the patient was situated during the remaining part of the procedure. Patients received a planning MRI (MRI-1) - a transversal T2-weigted turbo spin-echo with 2 mm slice thickness and 1.2 x 1.49 resolution. MRI was repeated prior to and after HDR BT delivery (MRI-2 & MRI-3) to assess the needle positions. Time points of MRIs were noted for calculating duration between each MRI. MRI-2 and MRI-3 were co-registered to MRI-1 to match the prostate, and needle migration was quantified for each needle in steps of 2 mm, equal to the image slice thickness. An average needle migration of !3 mm was considered ‘‘acceptable’’. Movement of the template relative to the ink markings was regarded as needle migration, which was evaluated on patient photos taken after each MRI and scored as either ‘‘acceptable’’ or ‘‘considerable’’ from MRI-1 to MRI-2 and from MRI-1 to MRI-3. Needle migration evaluated by either MRI or photos was compared. Results: A median of 16 needles (14-18) were used for each HDR-BT procedure. Serial photos were taken in 9/10 procedures. MRI-2 was performed in 10/10 procedures and MRI-3 in 8/10 procedures. Duration from MRI-1 to MRI-2 was median 1.1 h (0.8-1.7) and from MRI-2 to MRI-3 median 1.0 h (0.4- 1.4). MRI evaluated needle migration was median 1.7 mm per needle (0.3-2.4) from MRI-1 to MRI-2, median 2.1 mm per needle (1.3-5.6) from MRI-2 to MRI-3, and median 3.2 mm per

Figure 1. Top panels show serial photos of the needle implant in a patient. Each photo was taken just after the corresponding MRI below. Note the developing oedema of the perineum. Lower panels show serial sagital MR images of the prostate (in red) and needle implant. Needle tips of two needles are marked with arrows.

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needle (1.9-7.7) from MRI-1 to MRI-3. Needle migration velocity was in average 1.4 mm/h from MRI-1 to MRI-2 and 2.9 mm/h from MRI-2 to MRI-3. MRI evaluated needle migration was found ‘‘acceptable’’ in 10/ 10 procedures from MRI-1 to MRI-2, and in 4/8 procedures measured from MRI-1 to MRI-3. Photo evaluated needle migration was found ‘‘acceptable’’ in 9/9 procedures from MRI-1 to MRI-2 and in 5/7 procedures from MRI-1 to MRI-3. Concordance between MRI and photo evaluated needle migration was found in 15/16 evaluations. In one patient, photos showed a stable implant, but MRI revealed a considerable needle migration of average 5.9 mm per needle (Fig.1), possibly caused by oedema. Conclusions: Needle migration was of acceptable magnitude measured from MRI-1 to MRI-2, but of considerable magnitude from MRI-1 to MRI-3. Time dependent factors like oedema may explain this, but the higher migration velocity from MRI-2 to MRI-3 indicates that handling of the needle implant in relation to HDR-BT delivery is of more importance. Visual evaluation of template and needles may be an efficient method for detecting needle migration and deciding if re-imaging is necessary for replanning.

PO168 The Brachytherapy ‘‘Bermuda Triangle’’: A Potential Space with Important Implications for LDR and HDR Prostate Brachytherapy Payal D. Soni, MD1, Bin Yao, MS2, Cheryl Evans, MS2, Ahmed E. Abugharib, MD3, Vrinda Narayana, PhD2, Patrick W. McLaughlin, MD1,2. 1 Radiation Oncology, University of Michigan, Ann Arbor, MI, USA; 2 Radiation Oncology, Providence Cancer Center, Novi, MI, USA; 3 Department of Oncology, Sohag University, Sohag, Egypt. Purpose: Rectal toxicity is well-documented in the treatment of prostate cancer with brachytherapy. The rate of rectal toxicity is directly related to the distance between the rectum and the prostate and the ability to limit dose to the rectum. Typically the rectum abuts the prostate entirely along the posterior border as evidenced on computed tomography (CT) and magnetic resonance imaging (MRI) of the pelvis. However during implantation, while a rectal ultrasound probe is in place, we have observed that the rectum is often straightened and pulled away from the prostate. This distorts the anatomy by deforming the prostate, stretching the rectal wall, and often creating a temporary space and the illusion of distance between prostate and rectum during treatment planning. (Figure 1) Furthermore, this space can vary significantly based on probe position. Here we characterize this space that we refer to as the Brachytherapy Bermuda Triangle and discuss the implications for low dose rate (LDR) and high dose rate (HDR) brachytherapy. Materials and Methods: Pre-implant 3T MRI and transrectal ultrasound images were obtained on 25 patients prior to undergoing prostate LDR brachytherapy at a single institution. The ultrasound images were taken in the operating room just prior to needle insertion. The probe position was determined by the brachytherapist to allow for optimal visualization of the prostate. The space between the prostate and rectum from the base of the prostate to the apex was contoured on axial slices of both imaging studies and the volume of this space was obtained. The ratio of these volumes (Vus/Vmr) was calculated. Results: Of the 25 patients, 16 were found to have a substantial increase in the space between the prostate and rectum secondary to probe placement. The volume of this space increased by a factor of 1.7 to 29.3, when compared to the patient’s natural anatomy on MRI. In the remaining 9 patients, the space remained the same or became smaller by a factor of 0.5 to 1. The difference between each patient’s ultrasound and MRI volumes ranged from -2.54 cm3 to þ5.9cm3. The degree of change was noted to correlate with the probe position. Conclusions: During prostate brachytherapy while a rectal ultrasound probe is in place, there is an evident change in the male pelvic anatomy including the creation of a transient space between the prostate and rectum with important dosimetric implications. In permanent seed implants, if seeds are dropped in the Bermuda triangle or along the posterior edge of the prostate, the dose to the rectum will effectively be

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much higher than what is depicted on an ultrasound plan, as the rectum will ultimately recoil into this space upon removal of the probe. For temporary implants, this space can be exploited by moving the probe posteriorly during the actual treatment to minimize dose to the rectum. Awareness of the Bermuda triangle will allow brachytherapists to optimize setup and treatment planning to protect the rectum.

PO169 The Results of Permanent Prostate Brachytherapy with High Dose (D90% O 200 Gy) for Prostate Cancer Koji Inaba, MD, PhD, Keisuke Tsuchida, MD, Tairo Kashihara, MD, Kazuma Kobayashi, MD, Ken Harada, MD, PhD, Kana Takahashi, MD, Rei Umezawa, MD, PhD, Naoya Murakami, MD, PhD, Hiroshi Igaki, MD, PhD, Yoshinori Ito, MD, Jun Itami, MD, PhD. Department of Radiation Oncology, National Cancer Center Hospital, Tokyo, Japan. Purpose: ABS guideline suggests the appropriate prescription dose of I-125 for prostate cancer lies 140-160 Gy. There is a report D90% between 180 Gy and 200 Gy seem to be well tolerated with no increased incidence of toxicity. Further dose escalation is controversial; therefore, this study was conducted to examine the results of permanent prostate brachytherapy with high dose (D90% O 200 Gy) for prostate cancer. Materials and Methods: The database of our department found 46 patients who were treated with I-125 permanent prostate brachytherapy alone and the dose of D90% O 200 Gy. The analysis of patients’ characteristics, treatment, and results was performed. The median age was 67 years (range, 51-81). Three patients were classified to low-risk, 40 to intermediate-risk, 3 to high-risk. The median D90% was 215 Gy (interquartile range, 206-228). Results: The 5 year PSA recurrence-free survival and overall survival was 89.8% and 93.3%, respectively. V100% (160 Gy) for prostate was median 99.2% (interquartile range, 98.4-99.8), V150% for prostate was median 78.6% (interquartile range, 74.7-86.2), V100%(cc) for rectum was median 0.39 cc (interquartile range, 0.12-1.15). Severe adverse events equal to or more than Grade 3 was observed in only one patient with urethral stricture. Conclusions: The high dose of D90%O200 Gy seemed to be tolerable. The study to examine whether dose escalation improves the PSA control is needed.

PO170 Randomized Control Trial between HDR Brachytherapy and Intensity Modulated Radiotherapy in Localized Prostate Cancer: Analysis of Acute and Late Toxicity and Health Related Quality of Life Manikandan Annamalai, MBBS, Haresh Kunhiparambath, MD, DNB, Laviraj Ma, MSc, Sharma Dayanand, MD, Gupta Subhash, MD, Julka PK, MD, Rath GK, MD. Radiation Oncology, All India Institute of Medical Sciences, New Delhi, India. Purpose: Radical radiation with neo adjuvant, concurrent and adjuvant hormonal therapy is considered the standard of care for intermediate and high risk prostate cancer. Dose escalation by Intensity Modulated Radiotherapy (IMRT) or High dose rate brachytherapy (HDR-BT) significantly improves biochemical control in prostate cancer. In this prospective randomized study, we compared acute and late genitourinary (GU), gastrointestinal toxicity (GI) and health related quality of life between HDR-BT and IMRT. Materials and Methods: Thirty patients with localized prostate cancer were randomized to receive IMRT alone or IMRT plus HDR-BT. In phase I, all patients received EBRT 45Gy/25#/5 weeks by IMRT. In phase II patients received either HDR-BT 19Gy/2#/1implant or IMRT 29Gy/15#/ 3weeks. The IMRT planning was done in ADAC Pinnacle version 8.0M and treated with Synergy S. The brachytherapy was planned in Oncentra-

brachy version 4.3. GU and GI toxicity were assessed using CTCAE version 4.03 at 1, 3 and 6 months after treatment. Quality of life (EORTC QLQ PR-25) was assessed at baseline, 1, 3 and 6 months after treatment. Results: The median age, stage distribution, Gleason score, PSA and prostate volume of the cohort were 67.5 years, T2b-T3b, 7, 34.9ng/ml and 49.2cc respectively. On comparing acute toxicity between HDR-BT vs. IMRT, dysuria, increased urinary frequency, gastrointestinal toxicity were 33% vs. 40% (p!0.591), 40% vs. 46% (p!0.279) and 20% vs. 33% (p! 0.137) respectively. Any late genitourinary and gastrointestinal toxicity (grade $2) were 33% vs. 46% (p!0.280) and 6% vs. 20% (p!0.139) respectively. On comparing quality of life between the two arms, urinary scale (p!0.121), treatment scale (p!0.941) and sexual functioning scales (p!0.556) were comparable. However, bowel symptoms scale was better in HDR-BT arm (p!0.018). Conclusions: Incidence of acute GU and GI toxicity were comparable between IMRT and HDR-BT. Quality of life was also comparable between two modalities except gastrointestinal scale in which brachytherapy served better. Combined HDR-BT and EBRT may be preferred in localized prostate cancer as dose escalation is easily achievable.

PO171 An Examination of Clinical Outcomes in Patients Experiencing Biochemical Relapse in a Cohort of 966 Permanent Prostate Brachytherapy Monotherapy Patients Ryan Funk, MD, Lance Mynderse, MD, Wilson Torrence, MD, Christopher Deufel, PhD, Keith Furutani, PhD, Thomas Pisansky, MD, Michael Haddock, MD, Richard Choo, MD, Brian Davis, MD PhD. Mayo Clinic, Rochester, MN, USA. Purpose: Low rates of prostate specific antigen (PSA) relapse are observed following permanent prostate brachytherapy monotherapy (PPBM). We report a large single institution experience of outcomes following such relapse. Materials and Methods: We examined 966 consecutive pts treated with I125 PPBM between 4/98 and 1/13 with at least one post PPBM serum PSA to identify pts who experienced PSA relapse by the nadir þ 2 (Phoenix) criteria. Survival estimates used the Kaplan-Meier method. Results: Characteristics of the 966 pt cohort include median age of 69 years (range 42-86) and NCCN risk group of low (n5685, 71%) or intermediate (n5281, 29%). Overall survival (OS) at 5 and 10 years was 94% (95% confidence interval (CI) 92-95) and 74% (95% CI 69-78). Ten year prostate cancer-specific mortality (PCSM) was 2% (95% CI 0-3) overall and 1% (95% CI 0-3) vs 4% (95% CI 0-8, p50.02) for low vs intermediate risk prostate cancer. Freedom from PSA relapse at 5 and 10 years is 97% (95% CI 95-98) and 85% (95% CI 80-90). PSA relapse was detected in 45 pts at a median of 52 (IQR 36-67) months after PPBM with a median PSA at relapse of 3.9 (IQR 2.7-6) ng/dL. Characteristics of pts with relapse include NCCN low risk (n520) or intermediate risk (n525) at initial diagnosis. Relapse was found to be local (n5 10, 22%), nodal (n59, 20%), local and nodal (n51, 2%), distant (n59, 20%), local and distant (n51, 2%) or biochemical only (n515, 33%). Positive prostate biopsy was found in 12 of 23 (52%) (representing 12 local relapses in 966 pts (1.2%)). Biopsy pathology showed the same Gleason score (n53), higher Gleason score (n58) or new neuroendocrine features (n51) compared to initial diagnosis. Locoregional salvage therapy for local and/or nodal relapse was prostatectomy and lymph node dissection (n54), external beam radiotherapy (n52), cryotherapy (n51) or no local treatment (n513). Locoregional therapy without (n53) androgen deprivation therapy (ADT) resulted in persistent PSA in 1 pt and undetectable PSA for O72 months in 2 pts. Locoregional therapy with ADT (n54) resulted in PSA relapse in 1 pt at 36 months following salvage treatment and no PSA relapse at 5, 7 and 21 months in the remaining pts. ADT was given to 28 pts a median of 6 (IQR 3-17) months after PSA relapse with subsequent PSA decline in all pts. Median time to disease progression after ADT initiation was 36 months. One patient was treated with chemotherapy (carboplatin) as the initial management