Arthur Y. Hung

A comparison of CT scan to transrectal ultrasound-measured prostate volume in untreated prostate cancer☆

PURPOSE To compare CT and transrectal ultrasound (TRUS)-measured prostate volumes in patients with untreated prostate cancer. METHODS AND MATERIALS Between 1995 and 1999, 48 consecutive patients at the Portland Veterans Affairs Medical Center were treated with external beam radiotherapy. In 36 of these patients, TRUS and CT measurements of the prostate volume were obtained before treatment and <6 months apart. The TRUS volume was calculated using the prolate ellipsoid formula. The CT volume was calculated from the contours of the prostate drawn by one physician, who was unaware of the TRUS volume calculation, on axial CT images. RESULTS The TRUS and CT prostate volume measurements correlated strongly (Pearsons correlation coefficient = 0.925, 95% confidence interval 0.856-0.961, p < 0.0001). The CT volume was consistently larger than the TRUS volume by a factor of approximately 1.5. In men with a TRUS prostate volume less than the median (<28 cm(3)), the CT/TRUS volume ratio was 1.7, and it was 1.4 for men whose volume was greater than the median. The CT volumes were correlated similarly with the TRUS volumes regardless of the CT slice interval. CONCLUSION A strong correlation was found between CT scan and TRUS measurement of the prostate volume; however, CT consistently overestimated the prostate volume by approximately 50% compared with TRUS.

ASSESSMENT OF PLANNING TARGET VOLUME MARGINS FOR INTENSITY-MODULATED RADIOTHERAPY OF THE PROSTATE GLAND: ROLE OF DAILY INTER- AND INTRAFRACTION MOTION

PURPOSE To determine planning target volume margins for prostate intensity-modulated radiotherapy based on inter- and intrafraction motion using four daily localization techniques: three-point skin mark alignment, volumetric imaging with bony landmark registration, volumetric imaging with implanted fiducial marker registration, and implanted electromagnetic transponders (beacons) detection. METHODS AND MATERIALS Fourteen patients who underwent definitive intensity-modulated radiotherapy for prostate cancer formed the basis of this study. Each patient was implanted with three electromagnetic transponders and underwent a course of 39 treatment fractions. Daily localization was based on three-point skin mark alignment followed by transponder detection and patient repositioning. Transponder positioning was verified by volumetric imaging with cone-beam computed tomography of the pelvis. Relative motion between the prostate gland and bony anatomy was quantified by offline analyses of daily cone-beam computed tomography. Intratreatment organ motion was monitored continuously by the Calypso® System for quantification of intrafraction setup error. RESULTS As expected, setup error (that is, inter- plus intrafraction motion, unless otherwise stated) was largest with skin mark alignment, requiring margins of 7.5 mm, 11.4 mm, and 16.3 mm, in the lateral (LR), longitudinal (SI), and vertical (AP) directions, respectively. Margin requirements accounting for intrafraction motion were smallest for transponder detection localization techniques, requiring margins of 1.4 mm (LR), 2.6 mm (SI), and 2.3 mm (AP). Bony anatomy alignment required 2.1 mm (LR), 9.4 mm (SI), and 10.5 mm (AP), whereas image-guided marker alignment required 2.8 mm (LR), 3.7 mm (SI), and 3.2 mm (AP). No marker migration was observed in the cohort. CONCLUSION Clinically feasible, rapid, and reliable tools such as the electromagnetic transponder detection system for pretreatment target localization and, subsequently, intratreatment target location monitoring allow clinicians to reduce irradiated volumes and facilitate safe dose escalation, where appropriate.

Chemoradiation for adenocarcinoma of the anus.

PURPOSE To assess the efficacy and limitations of definitive chemoradiation for adenocarcinoma of the anal canal and to propose a treatment strategy that addresses the limitations of treatment. METHODS AND MATERIALS Between 1976 and 1998, 16 patients with localized adenocarcinoma of the anal canal were treated with radiotherapy with or without chemotherapy with curative intent. Available histologic slides were reviewed for evidence of primary adenocarcinoma of anal duct origin. The treatment results for these patients were compared with those of a group of patients with epidermoid histologic features who were all treated with definitive chemoradiation (55 Gy with concurrent 5-fluorouracil and cisplatin, n = 92) between 1989 and 1998. The hospital records were reviewed for all patients. Patients with epidermoid carcinoma presented with more advanced primary tumors (42% vs. 19% Stage T3 or greater). All adenocarcinoma patients were treated with radiotherapy (median dose 55 Gy): 11 received concurrent 5-fluorouracil-based chemotherapy and 5 received radiotherapy alone. The initial surgical procedures included abdominoperineal resection, excisional biopsies (n = 5), and local excision (n = 1). Abdominoperineal resection was performed as salvage therapy after local recurrence in 5 patients. The Kaplan-Meier method was used to calculate 5-year actuarial pelvic control, distant disease control, disease-free survival, and overall survival. The median follow-up was 45 months (range 5-196) for patients with adenocarcinoma and 44 months (range 9-115) for patients with epidermoid histologic features. RESULTS Both local and distant recurrence rates were significantly greater in the adenocarcinoma patients. Of 16 patients with adenocarcinoma, 7 (5-year actuarial rate 54%) had recurrence at the primary site compared with 16 (5-year actuarial rate 18%) of 92 patients with epidermoid histologic features (p = 0.004). Distant disease developed in more patients with adenocarcinoma (5-year actuarial rate 66%) than in patients with epidermoid carcinoma (5-year actuarial rate 10%, p <0.001). The 5-year actuarial disease-free survival and overall survival rate for adenocarcinoma patients was 19% and 64%, respectively, compared with 77% (p <0.0001) and 85% (p = 0.017) for those with epidermoid carcinoma. CONCLUSION Patients with localized adenocarcinoma of the anus treated with definitive chemoradiation had high rates of pelvic failure and distant metastasis compared with comparably staged patients with epidermoid histologic features treated similarly. On the basis of these limitations, we recommend preoperative chemoradiation followed by abdominoperineal resection to maximize pelvic disease control and consideration of adjuvant chemotherapy to address the problem of micrometastatic disease.

Phase I Trial of Preoperative Chemoradiation Plus Sorafenib for High Risk Extremity Soft Tissue Sarcomas with Dynamic Contrast-Enhanced MRI Correlates

Purpose: We conducted a phase I trial of the addition of sorafenib to a chemoradiotherapy regimen in patients with high-risk (intermediate/high grade, >5 cm) extremity soft tissue sarcoma undergoing limb salvage surgery. We conducted a correlative study of quantitative dynamic contrast-enhanced MRI (DCE-MRI) to assess response to treatment. Experimental Design: Patients were treated at increasing dose levels of sorafenib (200 mg daily, 400 mg daily, 400 mg twice daily) initiated 14 days before three preoperative and three postoperative cycles of epirubicin/ifosfamide. Radiation (28 Gy) was administered during cycle 2 with epirubicin omitted. The primary objective was to determine the maximum tolerated dose (MTD) of sorafenib. DCE-MRI was conducted at baseline, after 2 weeks of sorafenib, and before surgery. The imaging data were subjected to quantitative pharmacokinetic analyses. Results: Eighteen subjects were enrolled, of which 16 were evaluable. The MTD of sorafenib was 400 mg daily. Common grade 3–4 adverse events included neutropenia (94%), hypophosphatemia (75%), anemia (69%), thrombocytopenia (50%), and neutropenic fever/infection (50%). Of note, 38% developed wound complications requiring surgical intervention. The rate of ≥95% histopathologic tumor necrosis was 44%. Changes in DCE-MRI biomarker ΔKtrans after 2 weeks of sorafenib correlated with histologic response (R2 = 0.67, P = 0.012) at surgery. Conclusion: The addition of sorafenib to preoperative chemoradiotherapy is feasible and warrants further investigation in a larger trial. DCE-MRI detected changes in tumor perfusion after 2 weeks of sorafenib and may be a minimally invasive tool for rapid assessment of drug effect in soft tissue sarcoma. Clin Cancer Res; 19(24); 6902–11. ©2013 AACR.

Histologic response of dose-intense chemotherapy with preoperative hypofractionated radiotherapy for patients with high-risk soft tissue sarcomas

The authors studied a dose‐intense regimen of epirubicin and ifosfamide with hypofractionated preoperative radiotherapy for high‐risk soft tissue sarcomas. The primary objective was estimation of the rate of ≥95% pathologic necrosis.

Incorporating priors for medical image segmentation using a genetic algorithm

Medical image segmentation is typically performed manually by a physician to delineate gross tumor volumes for treatment planning and diagnosis. Manual segmentation is performed by medical experts using prior knowledge of organ shapes and locations but is prone to reader subjectivity and inconsistency. Automating the process is challenging due to poor tissue contrast and ill-defined organ/tissue boundaries in medical images. This paper presents a genetic algorithm for combining representations of learned information such as known shapes, regional properties and relative position of objects into a single framework to perform automated three-dimensional segmentation. The algorithm has been tested for prostate segmentation on pelvic computed tomography and magnetic resonance images.

Real-time prostate motion assessment: image-guidance and the temporal dependence of intra-fraction motion.

BackgroundThe rapid adoption of image-guidance in prostate intensity-modulated radiotherapy (IMRT) results in longer treatment times, which may result in larger intrafraction motion, thereby negating the advantage of image-guidance. This study aims to qualify and quantify the contribution of image-guidance to the temporal dependence of intrafraction motion during prostate IMRT.MethodsOne-hundred and forty-three patients who underwent conventional IMRT (n=67) or intensity-modulated arc therapy (IMAT/RapidArc, n=76) for localized prostate cancer were evaluated. Intrafraction motion assessment was based on continuous RL (lateral), SI (longitudinal), and AP (vertical) positional detection of electromagnetic transponders at 10 Hz. Daily motion amplitudes were reported as session mean, median, and root-mean-square (RMS) displacements. Temporal effect was evaluated by categorizing treatment sessions into 4 different classes: IMRTc (transponder only localization), IMRTcc (transponder + CBCT localization), IMATc (transponder only localization), or IMATcc (transponder + CBCT localization).ResultsMean/median session times were 4.15/3.99 min (IMATc), 12.74/12.19 min (IMATcc), 5.99/5.77 min (IMRTc), and 12.98/12.39 min (IMRTcc), with significant pair-wise difference (p<0.0001) between all category combinations except for IMRTcc vs. IMATcc (p>0.05). Median intrafraction motion difference between CBCT and non-CBCT categories strongly correlated with time for RMS (t-value=17.29; p<0.0001), SI (t-value=−4.25; p<0.0001), and AP (t-value=2.76; p<0.0066), with a weak correlation for RL (t-value=1.67; p=0.0971). Treatment time reduction with non-CBCT treatment categories showed reductions in the observed intrafraction motion: systematic error (Σ)<0.6 mm and random error (σ)<1.2 mm compared with ≤0.8 mm and <1.6 mm, respectively, for CBCT-involved treatment categories.ConclusionsFor treatment durations >4-6 minutes, and without any intrafraction motion mitigation protocol in place, patient repositioning is recommended, with at least the acquisition of the lateral component of an orthogonal image pair in the absence of volumetric imaging.

MINIMAL BENEFIT OF AN ENDORECTAL BALLOON FOR PROSTATE IMMOBILIZATION AS VERIFIED BY DAILY LOCALIZATION

We wanted to investigate whether using an endorectal balloon (ERB) in lieu of image guidance is reasonable. We compared daily prostate motion in 2 cohorts of patients with fiducial markers implanted in the prostate, one group with the ERB and the other without. Twenty-nine patients were treated using intensity-modulated radiation therapy: 14 with an ERB, and 15 without. All had fiducial markers placed in the prostate. We reviewed the daily displacements necessary to place the isocenter on the prostate as determined by portal imaging. In addition, we used the data to determine whether there is a change in prostate motion over the treatment course. The average prostate displacement for patients treated without an ERB was slightly greater than the average displacement for patients treated with the ERB. However, the difference observed with the ERB was not statistically significant (p > 0.05). The margins necessary to encompass the prostate 95% of the time for the patients treated without an ERB in the lateral, cranio/caudal, and anterior/posterior dimensions would be 4.8, 12.1, and 15.2 mm, respectively. When using the ERB, the margins necessary would be 4.1, 10.4, and 11 mm, respectively. Prostate motion in the anterior-posterior direction actually increased over the course of treatment in patients without an ERB. This increase was prevented by use of the ERB. Day-to-day variability of the position of the prostate is reduced in all dimensions with the water-filled ERB, but not significantly statistically. Use of the water-filled ERB did not obviate performing some form of image guidance daily.

Pelvic applications of MR-guided high intensity focused ultrasound

MR-guided high intensity focused ultrasound (MRg HIFU) is a novel method of tissue ablation that incorporates high energy focused ultrasound for tissue heating and necrosis within an MR scanner that provides simultaneous stereotactic tissue targeting and thermometry. To date, MRg HIFU has been used primarily to treat uterine fibroids, but many additional applications in the pelvis are in development. This article reviews the basic technology of MRg HIFU, and the use of MRg HIFU to treat uterine fibroids, adenomyosis, and prostate cancer.

Contemporary Management of High-risk Localized Prostate Cancer

The management of high-risk, localized prostate cancer remains a formidable challenge despite significant technical advances in surgery and radiation therapy. Treatment outcomes of radiation therapy are improved by the addition of adjuvant androgen deprivation therapy, whereas, with surgery, oncologic results are enhanced with either postoperative radiation therapy or androgen deprivation therapy in select cases. In high-risk prostate cancer, disease recurrence after primary therapy may occur at either distant or local sites. Ongoing studies are in the process of evaluating systemic therapy for the eradication of local and micrometastatic disease. Neoadjuvant therapies offer the opportunity to maximize local control as a path to improved outcomes and critically evaluate agent effectiveness in the target tissue. The treatment for high-risk localized prostate cancer is in evolution. It is likely that the development of effective strategies based on understanding prostate tumor biology will lead to significant advances in the treatment of this disease.