W. Foster

Dosimetric Impact of Interfraction Catheter Movement in High-Dose Rate Prostate Brachytherapy

PURPOSE To evaluate the impact of interfraction catheter movement on dosimetry in prostate high-dose-rate (HDR) brachytherapy. METHODS AND MATERIALS Fifteen patients were treated with fractionated HDR brachytherapy. Implants were performed on day 1 under transrectal ultrasound guidance. A computed tomography (CT) scan was performed. Inverse planning simulated annealing was used for treatment planning. The first fraction was delivered on day 1. A cone beam CT (CBCT) was performed on day 2 before the second fraction was given. A fusion of the CBCT and CT was performed using intraprostatic gold markers as landmarks. Initial prostate and urethra contours were transferred to the CBCT images. Bladder and rectum contours were drawn, and catheters were digitized on the CBCT. The planned treatment was applied to the CBCT dataset, and dosimetry was analyzed and compared to the initial dose distribution. This process was repeated after a reoptimization was performed, using the same constraints used on day 1. RESULTS Mean interfraction catheter displacement was 5.1 mm. When we used the initial plan on day 2, the mean prostate V100 (volume receiving 100 Gy or more) decreased from 93.8% to 76.2% (p < 0.01). Rectal V75 went from 0.75 cm(3) to 1.49 cm(3) (p < 0.01). A reoptimization resulted in a mean prostate V100 of 88.1%, closer to the initial plan (p = 0.05). Mean rectal V75 was also improved with a value of 0.59 cm(3). There was no significant change in bladder and urethra dose on day 2. CONCLUSIONS A mean interfraction catheter displacement of 5.1 mm results in a significant decrease in prostate V100 and an increase in rectum dose. A reoptimization before the second treatment improves dose distribution.

Identification of Sequence Determinants That Direct Different Intracellular Folding Pathways for Aquaporin-1 and Aquaporin-4

Homologous aquaporin water channels utilize different folding pathways to acquire their transmembrane (TM) topology in the endoplasmic reticulum (ER). AQP4 acquires each of its six TM segments via cotranslational translocation events, whereas AQP1 is initially synthesized with four TM segments and subsequently converted into a six membrane-spanning topology. To identify sequence determinants responsible for these pathways, peptide segments from AQP1 and AQP4 were systematically exchanged. Chimeric proteins were then truncated, fused to a C-terminal translocation reporter, and topology was analyzed by protease accessibility. In each chimeric context, TM1 initiated ER targeting and translocation. However, AQP4-TM2 cotranslationally terminated translocation, while AQP1-TM2 failed to terminate translocation and passed into the ER lumen. This difference in stop transfer activity was due to two residues that altered both the length and hydrophobicity of TM2 (Asn49 and Lys51 in AQP1 versus Met48 and Leu50 in AQP4). A second peptide region was identified within the TM3–4 peptide loop that enabled AQP4-TM3 but not AQP1-TM3 to reinitiate translocation and cotranslationally span the membrane. Based on these findings, it was possible to convert AQP1 into a cotranslational biogenesis mode similar to that of AQP4 by substituting just two peptide regions at the N terminus of TM2 and the C terminus of TM3. Interestingly, each of these substitutions disrupted water channel activity. These data thus establish the structural basis for different AQP folding pathways and provide evidence that variations in cotranslational folding enable polytopic proteins to acquire and/or maintain primary sequence determinants necessary for function.

Cancer of the Penis

Penile cancer is rare in Western countries (<1% of cancers in men), but accounts for 10–20% of male malignancies in Africa, Asia, and South America. LN drainage: skin of penis – bilateral superficial inguinal nodes; glans penis – bilateral inguinal or iliac nodes; penis corporal tissue – bilateral deep inguinal and iliac; 20% chance of LN+ at surgery if clinically node negative. Risk factors: uncircumcised status, phimosis, poor local hygiene, HPV-16, 18. Pathology: 95% squamous cell; others very rare – melanoma, lymphoma, basal cell, Kaposi’s sarcoma.

SU‐FF‐T‐69: An Inter‐Fraction Adaptive Strategy for High‐Dose Rate Prostate Brachytherapy

Purpose: To determine the dosimetric impact of interfraction organ‐catheter displacements and settle on an adaptive strategy to maintain the quality of the implant. Methods & Material: 10 patients received HDR prostate implants on Day‐1 with CT‐based dose plan optimized with the inverse planning tool IPSA to deliver the first of two fractions of 9.5 Gy. On Day‐2 before the second fraction, a CBCT was acquired and fused with the Day‐1 CT. Initial prostate and urethra contours were transferred to CBCTimages. Bladder and rectum contours were drawn and catheters digitized on the CBCT. Day‐1 dwell times were applied to the CBCT dataset. The plan was also re‐optimized with IPSA using the volumes from CT, catheters from CBCT, and the same constraints as Day‐1. The same physician re‐contoured the prostate and urethra on CBCT, and two new plans were obtained as above. Four adaptive scenarios per patient were thus created with the CBCTimages, using initial/new contours with initial/new plannings. For each strategy, the prostate V100 and V150, urethra V120, bladder and rectum V75 from Day‐2 were compared to Day‐1. Results: Relative organ‐to‐catheter displacements on Day‐2 cause prostate V100 to decrease and dose to other organs to increase as compared to Day‐1. Relative organ‐catheter displacements of more than 6 mm can be used to trigger a replanning. Among adaptive strategies, re‐optimizing the plan with the catheters defined on the CBCT was found sufficient to maintain the quality of the implant, while minimizing workload increase. Conclusion: Visual inspection of catheters on fused CBCT‐CT allows for an accurate and rapid evaluation of the integrity of the implant. When replanning is required, dwell times can be reoptimized using the catheters defined on CBCT, insuring that all dosimetric indices are within required values at each delivered fraction. This work is supported in part by Nucletron.

138 Intra-operative treatment planning: A way to improve dosimetry in prostate brachytherapy

Purpose: To demonstrate the advantage of intra-operative (IO) over pre-operative planning by evaluating the impact of patients position on urethra and prostate dosimetry after I125 implant. Material and Methods: Real time dosimetry of a group of 15 patients treated with I125 permanent prostate implant was evaluated with changing leg arid/or urethras position. 3D ultrasound was used to plan seed implantation. Scans were repeated after downward movements of patients urethra and legs. The initial IO clinical plans were applied to these new scans. Doses to urethra (D5, V150) and prostate (D90, V200) were compared for the different positions. Results: The mean value of prostates D90 went from 194, 2 Gy to 172, 5 Gy after a urinary catheter displacement (p=0.001) and to 170, 2 Gy when legs were moved. The maximal urethras D5 variation observed for each patient ranged from 4, 2 to 70, 7%, with a mean increase of 26, 6%. A third of the patients (5/15) presented values of urethras D5 beyond 300 Gy. A mean 17, 7% variation of the urethras V150 was observed for the 15 patients, going from an initial 8,1% to 22,8% with a displacement of the urethra (p=0.024) and to 28, 7% when moving the legs (p=0.001). Conclusions: Patient positioning has an impact on dosimetry. We observed a significant decrease of the prostates D90 and V200 combined with a significant increase of urethras D5 and V150 when moving patients legs and even the urethra catheter. This translates in a clear dosimetric advantage of intraoperative dosimetry over pre-planning.