Peter Grimm

A Kinetic Evaluation of Blood—Brain Barrier Permeability in Human Brain Tumors with [68Ga]EDTA and Positron Computed Tomography

Twelve patients with primary and metastatic brain tumors were evaluated with [68Ga]ethylenediaminetetraacetate (EDTA) and positron computed tomography. Using a two-compartment tracer kinetic model, foward (K1) and reverse (k2) rate constants for molecular diffusion across the blood–brain barrier (BBB) were obtained and averaged 0.0029 ± 0.0016 (mean ± SD) ml/min/g for K1 and 0.0310 ± 0.0156 min−1 for k2. Most tracer kinetic models are based on the assumption that tissue radioactivity contains no vascular component or require independent measures of cerebral blood volume (CBV) which are then subtracted from the measure tissue activity. The model in this work differs from that approach by assuming a vascular compartment in the tissue kinetic data. This vascular parameter is estimated from sequential measurements of activity concentrations in regions with an intact BBB or from measurements of 68Ga concentrations in the plasma (the input function). Thus, this approach does not require the assumption of a zero vascular contribution, does not require a separate measurement of CBV, and uses the criteria of constrained estimation to provide estimates of the local CBV and molecular diffusion through the BBB. Estimates of the relative CBV of the lesions in four studies (three subjects) with [68Ga]EDTA correlated well with those obtained with the C15O hemoglobin technique (correlation coefficient of 0.97).

Permanent prostate brachytherapy preplanned technique: The modern Seattle method step-by-step and dosimetric outcomes

PURPOSE To describe, step-by-step, the current Seattle preplan technique, and report the dosimetric outcomes on 1,131 consecutively such treated prostate brachytherapy patients. METHODS AND MATERIALS One thousand one hundred thirty one patients with prostate cancer were treated with iodine-125 ((125)I), palladium-103 ((103)Pd), or cesium-131 ((131)Cs) using a preplanned template-guided transrectal ultrasound-guided approach between January 2005 and August 2007. Day one computed tomography (CT) scans were taken for postimplantation dose-volume histogram evaluations. Postoperative prostate contours were drawn by one author (DN) on CT images taken on postoperative day one. RESULTS The volume of prostate receiving 100% of prescription dose (V(100)) and percent dose to 90% of the prostate (%D(90)) were 95% and 106% for 558 monotherapy (125)I implants, 91% and 102% for 327 (103)Pd implants, and 97% and 111.5% for 13 (131)Cs implants, respectively. The median V(100) and percent D(90) were 91% and 101% for five boost (125)I implants, 92% and 104% for 228 boost (103)Pd implants. The median rectal volume receiving 100% of prescription dose (RV(100)) for (125)I, (103)Pd, and (131)Cs monotherapy implants were 0.3, 0.13, and 0.38cc, and for (125)I and (103)Pd boost implants were 0.16 and 0.13cc, respectively. No patient received an RV(100) of >0.92cc. CONCLUSIONS Modern preplanned template and ultrasound-guided prostate brachytherapy can consistently result in excellent prostate dosimetry and rectal sparing.

Contralateral breast cancers following treatment for initial breast cancers in women

The risk of a second primary cancer arising in the contralateral breast following treatment of an initial breast cancer was evaluated for 1,630 women whose first breast cancers were diagnosed and treated at University of California at Los Angeles between 1955 and 1979. Based on follow-up data ranging from 5 to 30 years, the rate of development of nonsimultaneous contralateral breast cancers was slightly in excess of 2.5 per 1,000 person-years at risk. There was no detectably significant difference in the frequency of second primary cancers related to the type of treatment of the first cancers, whether that was surgery, radiation therapy, or surgery plus radiation therapy.

First report on the use of a thinner 125I radioactive seed within 20-gauge needles for permanent radioactive seed prostate brachytherapy: Evaluation of postimplant dosimetry and acute toxicity

PURPOSE To compare postoperative dosimetry and acute toxicity of new 0.5-mm (125)I seeds in 20-gauge (20G) diameter prostate brachytherapy (PB) needles with standard 0.8-mm seeds in 18G needles. METHODS AND MATERIALS Postoperative dosimetry was performed on 100 consecutive PB patients treated with ThinSeeds in 20G needles and compared with 100 consecutively treated PB patients using standard-sized seeds and needles (18G). Dosimetry was performed on postoperative Day 1 CT scans. Acute urinary retention was also compared between these two groups. Acute toxicity was evaluated in 22 consecutively treated patients with thinner seeds/needles and compared with 22 consecutive concurrent patients treated with standard seeds and needles. All patients were evaluated by pre- and post-PB self-administered surveys, physical examinations on post-PB Day 1, and telephone surveys on Day 7. Endpoints included dysuria, acute urinary retention, hematuria, perineal pain/bruising, and International Prostate Symptom Score. RESULTS Post-PB dosimetric comparison demonstrated that the V100 (95% vs. 91%), D90 (161Gy vs.149Gy), V150 (55% vs. 45%), and RV100 (0.43cc vs. 0.30cc) were significantly (p<0.0004) higher in the 20G group. Urinary retention rates were 8% and 7% and median catheter-dependent durations were 7 and 14 days for the 20G and 18G groups, respectively. No significant differences were found for dysuria, hematuria, or International Prostate Symptom Score. Post-PB Day 1 perineal bruising and pain scores on Days 1 and 7 were significantly less (p<0.04) in 20G cohort. CONCLUSIONS Smaller diameter needles and seeds resulted in improved post-PB Day 1 V100 and D90 dosimetry, and significantly less acute perineal pain and bruising.

Analysis of the Pro-Qura Database: Rectal dose, implant quality, and brachytherapist's experience

PURPOSE This study analyzed rectal dosimetry outcomes of Pro-Qura proctored implants to assess the achievability of proposed rectal dose constraints in the setting of standardized pre- and postimplant dosimetry in community-based brachytherapy programs. METHODS AND MATERIALS From August 2005 to July 2007, 713 postimplant CT scans were evaluated from 26 brachytherapists actively participating in Pro-Qura. Postimplant dosimetry was performed in a standardized fashion. The entirety of the rectal wall was contoured and evaluated for dose. Rectal dose was defined in terms of the volume of the rectum receiving 100% of the prescription dose (R(100)). Criteria for implant adequacy for both (103)Pd and (125)I included a prostate the percentage of the prostate volume covered by the prescription dose (V(100))>80%, a prostate the maximum dose covering 90% of the prostate volume (D(90)) of 90-140%, and an R(100)<1.0cm(3) for early (Day 0-7) dosimetry and <1.3cm(3) for late (Day 20-45) dosimetry. RESULTS Mean prostatic volume was 35.1cm(3). The mean time from implant to CT scan was 29.9 days (range, 0-45 days). The respective mean overall prostate V(100) and D(90) were 89% and 101%, respectively, and remained consistent for sequence groups 1 through 6. Overall, the mean R(100) was 0.97+/-1.04cm(3). The R(100) was 1.15cm(3) for sequence Group 1 and with each subsequent sequence group decreased with a nadir of 0.83cm(3) in sequence Group 6 (p=0.22). Rectal dosimetry was deemed inadequate in 39% of Group 1 implants but only 22% in Group 6 (p=0.016). The reduced rectal doses did not impact prostate gland coverage. CONCLUSIONS Using standardized dosimetry, R(100) improved with increasing brachytherapists experience, reaching a plateau after approximately 20 patients.

Permanent prostate brachytherapy extracapsular radiation dose distributions: analysis of a multi-institutional database.

Purpose Periprostatic brachytherapy doses impact biochemical control. In this study, we evaluate extracapsular volumetric dosimetry following permanent prostate brachytherapy in patients entered in a multi-institutional community database. Material and methods In the database, 4547 patients underwent brachytherapy (3094 – 125I, 1437 – 103Pd and 16 – 131Cs). Using the originally determined prostate volume, a 5 mm, 3-dimensional peri-prostatic anulus was constructed around the prostate (except for a 2 mm posterior margin), and evaluated in its entirety and in 90° segments. Prostate dosimetric parameters consisted of a V100 and D90 while the annular dosimetry was reported as a V100. Results The intraprostatic V100 and D90 for 103Pd, and 125I were statistically comparable when stratified by isotope and/or monotherapy vs. boost. The overall mean V100 for the periprostatic annulus was 62.8%. The mean V100 at the base (51.6%) was substantially less than the apex (73.5%) and midgland (65.9%). In addition, for all patients, the anterior V100 (45.7%) was less than the lateral (68.8%) and the posterior (75.0%). The geometric V100 annular differences were consistent when evaluated by isotope. Overall, the V100 was higher in the 125I cohort. Conclusions The optimal extracapsular brachytherapy dose and radial extent remains unknown, but will prove increasingly important with reductions and/or elimination of supplemental external beam radiation therapy. The large multi-institutional community database demonstrates periprostatic annular doses that are not as robust as those in selected high volume brachytherapy centers, and may be inadequate for optimal biochemical control following monotherapeutic brachytherapy, especially in higher risk patients.

The Effect of Pro-Qura Case Volume on Post-Implant Prostate Dosimetry

PURPOSE To evaluate the effect of prostate brachytherapy case volume on postimplant dosimetric quality in Pro-Qura proctored programs. METHODS AND MATERIALS From August 1999 to December 2008, the computed tomography datasets for 6,600 prostate implants performed by 129 brachytherapists were submitted to Pro-Qura for dosimetric analysis. Brachytherapists were divided into three roughly equal-sized terciles based on total case volume. Postimplant computed tomography scans were obtained at a median of 30 days. Excellent target coverage was defined by a V100≥90% and D90≥100% minimum prescribed peripheral dose. To determine if the number of excellent implants improved with increasing case numbers, each brachytherapists series of implants was bisected into early and late experience by a moveable critical point. RESULTS For the entire cohort, the mean V100 and D90 were 89.2% and 102.8%, respectively, with 47.7% of the implants scored as excellent. Brachytherapists in the highest-case tercile had a significantly greater fraction of excellent target coverage (57.9%) than did those in the two lower terciles (39.5% and 45.7%, p=0.015). Twenty-one (25.6%) of the 82 brachytherapists with sufficient case volume for dosimetric improvement analyses demonstrated quality improvement over time. Although there was no significant difference between prostate volume and seed strength, the number of seeds used was significantly greater in adequate implants. CONCLUSIONS The highest-volume brachytherapists were most likely to obtain excellent target coverage. We are encouraged that in general practice, nearly 48% of all implants were scored excellent. It is conceivable that with greater expert third-party involvement, an even greater percentage of cases with excellent target coverage will become reality.

Impact of small prostate size on postimplant prostate dosimetry: Analysis of a large community database

PURPOSE Achieving high-quality permanent interstitial brachytherapy in smaller prostates is thought to be more difficult than in larger glands. This study evaluates 4547 implants in a large community database to test this hypothesis. METHODS AND MATERIALS From January 2003 to October 2010, 4547 prostate brachytherapy implants from a large community database were analyzed. The cohort was divided into three groups based on size, namely smaller (<30cm(3), n=1301), medium (30-40cm(3), n=1861), and large (>40cm(3), n=1385). Postimplant dosimetry, including D90, V100, and V100 by prostate sector, was performed for each implant. Comparison of mean V100 among small, medium, and larger prostate volume cohorts was performed using a one-way analysis of variance test. RESULTS For the overall cohort, the D90 was 105% and 104% for monotherapy and boost, respectively. Mean D90 for small prostates was 106% and 104% for monotherapy and boost, respectively. Mean V100 for small prostates was 91.1% and 90.0%, respectively. Coverage for small prostates was as good or slightly better than larger glands. V100 by prostate sector revealed that there were no sectors for which smaller glands had significantly inferior coverage compared with larger glands. CONCLUSION Although smaller prostates may in some respects be more technically difficult to implant than larger glands, a review of community-based brachytherapists reveals that with current implant techniques, good quality implants are readily achievable in men with smaller glands.

Transrectal Ultrasound-Guided Prostate Brachytherapy

The most common solid malignancy in men, prostate cancer is now being diagnosed, in most men, in the very earliest stages, in the United States (1). This surge in earlier-stage diagnosis is the result, in large part, of the introduction and increased use of the prostate-specific antigen (PSA) blood test (2). Traditional therapeutic options of radical prostatectomy and external beam radiation therapy have come under more scrutiny because PSA tests in follow-up reveal disease control rates have been found to be lower than previously thought (3–6). Neither radical prostatectomy nor external beam radiation therapy (EBRT) appear to result in superior cancer control, vs each other, when major pretreatment prognostic variables are taken into consideration (7–11). Moreover, patient-reported toxicity rates have been found to be considerably higher than the previous physician-reported rates (12).

Modern Prostate Brachytherapy

rostate cancer remains the most common solid cancer and the second leading cause of cancer death among American men. Although there was an initial, rapid rise in the incidence of prostate cancer diagnoses in the early 1990s following the development of the Prostate Specific Antigen (PSA) screening test, this “harvesting” effect is over. The incidence rate for prostate cancer is now nearly back to its pre-PSA era level.1,2 One significant and lasting result of the widespread adoption of the PSA test was the dramatic increase in the proportion of treatable, early-stage cancers found at the time of diagnosis. Prior to the availability of PSA testing, a majority of patients were diagnosed with more advanced, difficult-to-treat malignancies. Today, almost 80 percent of newly diagnosed patients have early-stage disease, which has a much higher probability of biochemical relapse-free survival. The other major contribution of the PSA test is its usefulness as a post-treatment monitoring tool that can detect recurrent disease much sooner than had previously been possible, and also tells physicians whether they have successfully treated the entire tumor or left residual disease behind. Early-stage cancers are usually amenable to treatment with conventional local therapies, radical prostatectomy, or external beam radiation therapy (EBRT) and, increasingly, with radioactive seed implantation, also known as transperineal interstitial permanent prostate brachytherapy (TIPPB). Over the past decade, the use of TIPPB has risen significantly for several reasons. First, research has clearly demonstrated that ultrasound-guided seed implantation, with its sophisticated instrumentation, treatment planning tools, and evaluation techniques, is as effective as other treatments in terms of long-term cancer control, and it has a low incidence of serious side effects and complications. In addition, the use of the PSA for follow-up evaluation has revealed that EBRT and radical prostatectomy are not as effective at eradicating prostate cancer as once thought.3-6 Another factor behind the rising interest in seed implantation has been the pressure of traditional market forces and, in particular, patient demand. Attracted by TIPPB’s outpatient orientation, rapid recovery time, low complication rate (especially with regard to impotence and incontinence), and favorable long-term survival rates, men and their families have been actively seeking out brachytherapy treatment and the physicians who provide it. One recent evaluation estimated that almost 50 percent of the men treated for prostate cancer used TIPPB as part of their treatment course1 (Figure 1).