Raywin Huang

Accelerated Treatment of Breast Cancer

PURPOSE Radiation therapy (RT) restricted to the tumor bed, by means of an interstitial implant, and lasting 4 to 5 days after lumpectomy was prospectively evaluated in early-stage breast cancer patients treated with breast-conserving therapy (BCT). The goals of the study were to determine whether treatment time can be reduced and whether elective treatment of the entire breast is necessary. MATERIALS AND METHODS Between January 1993 and January 2000, 174 cases of early-stage breast cancer were managed with lumpectomy followed by RT restricted to the tumor bed using an interstitial implant. Each brachytherapy patient was matched with one external-beam RT (ERT) patient derived from a reference group of 1,388 patients treated with standard BCT. Patients were matched for age, tumor size, histology, margins of excision, absence of an extensive intraductal component, nodal status, estrogen receptor status, and tamoxifen use. Median follow-up for both the ERT and brachytherapy groups was 36 months. RESULTS No statistically significant differences were noted in the 5-year actuarial rates of ipsilateral breast treatment failure or locoregional failure between ERT and brachytherapy patients (1% v 0%, P =.31 and 2% v 1%, P =.63, respectively). In addition, there were no statistically significant differences noted in rates of distant metastasis (6% v 3%, P =.24), disease-free survival (87% v 91%, P =.55), overall survival (90% v 93%, P =.66), or cause-specific survival (97% v 99%, P =.28). CONCLUSION Accelerated treatment of breast cancer using an interstitial implant to deliver radiation to the tumor bed alone over 4 to 5 days seems to produce 5-year results equivalent to those achieved with conventional ERT. Extended follow-up will be required to determine the long-term efficacy of this treatment approach.

Dose escalation using conformal high-dose-rate brachytherapy improves outcome in unfavorable prostate cancer

PURPOSE To overcome radioresistance for patients with unfavorable prostate cancer, a prospective trial of pelvic external beam irradiation (EBRT) interdigitated with dose-escalating conformal high-dose-rate (HDR) prostate brachytherapy was performed. METHODS AND MATERIALS Between November 1991 and August 2000, 207 patients were treated with 46 Gy pelvic EBRT and increasing HDR brachytherapy boost doses (5.50-11.5 Gy/fraction) during 5 weeks. The eligibility criteria were pretreatment prostate-specific antigen level >or=10.0 ng/mL, Gleason score >or=7, or clinical Stage T2b or higher. Patients were divided into 2 dose levels, low-dose biologically effective dose <93 Gy (58 patients) and high-dose biologically effective dose >93 Gy (149 patients). No patient received hormones. We used the American Society for Therapeutic Radiology and Oncology definition for biochemical failure. RESULTS The median age was 69 years. The mean follow-up for the group was 4.4 years, and for the low and high-dose levels, it was 7.0 and 3.4 years, respectively. The actuarial 5-year biochemical control rate was 74%, and the overall, cause-specific, and disease-free survival rate was 92%, 98%, and 68%, respectively. The 5-year biochemical control rate for the low-dose group was 52%; the rate for the high-dose group was 87% (p <0.001). Improvement occurred in the cause-specific survival in favor of the brachytherapy high-dose level (p = 0.014). On multivariate analysis, a low-dose level, higher Gleason score, and higher nadir value were associated with increased biochemical failure. The Radiation Therapy Oncology Group Grade 3 gastrointestinal/genitourinary complications ranged from 0.5% to 9%. The actuarial 5-year impotency rate was 51%. CONCLUSION Pelvic EBRT interdigitated with transrectal ultrasound-guided real-time conformal HDR prostate brachytherapy boost is both a precise dose delivery system and a very effective treatment for unfavorable prostate cancer. We demonstrated an incremental beneficial effect on biochemical control and cause-specific survival with higher doses. These results, coupled with the low risk of complications, the advantage of not being radioactive after implantation, and the real-time interactive planning, define a new standard for treatment.

The dose-volume realationship of acute small bowel toxicity from concurrent 5-FU-based chemotherapy and radiation therapy for rectal cancer

Abstract Purpose: A direct relationship between the volume of small bowel irradiated and the degree of acute small bowel toxicity experienced during concurrent 5-fluorouracil (5-FU)-based chemoradiotherapy for rectal carcinoma is well recognized but poorly quantified. This study uses three-dimensional treatment-planning tools to more precisely quantify this dose-volume relationship. Methods and Materials: Forty patients receiving concurrent 5-FU-based chemotherapy and pelvic irradiation for rectal carcinoma had treatment-planning CT scans with small bowel contrast. A median isocentric dose of 50.4 Gy was delivered using a posterior-anterior and opposed lateral field arrangement. Bowel exclusion techniques were routinely used, including prone treatment position on a vacuum bag cradle to allow anterior displacement of the abdominal contents and bladder distension. Individual loops of small bowel were contoured on each slice of the planning CT scan, and a small bowel dose-volume histogram was generated for the initial pelvis field receiving 45 Gy. The volume of small bowel receiving each dose between 5 and 40 Gy was recorded at 5-Gy intervals. Results: Ten patients (25%) experienced Common Toxicity Criteria Grade 3+ acute small bowel toxicity. A highly statistically significant association between the development of Grade 3+ acute small bowel toxicity and the volume of small bowel irradiated was found at each dose level. Specific dose-volume threshold levels were found, below which no Grade 3+ toxicity occurred and above which 50–60% of patients developed Grade 3+ toxicity. The volume of small bowel receiving at least 15 Gy ( V 15 ) was strongly associated with the degree of toxicity. Univariate analysis of patient and treatment-related factors revealed no other significant predictors of severe toxicity. Conclusions: A strong dose-volume relationship exists for the development of Grade 3+ acute small bowel toxicity in patients receiving concurrent 5-FU-based chemoradiotherapy for rectal carcinoma.

Does local recurrence affect the rate of distant metastases and survival in patients with early‐stage breast carcinoma treated with breast‐conserving therapy?

The purpose of the current analysis was to evaluate the impact of local recurrence (LR) on the development of distant metastases (DM), overall survival (OS), and cause specific survival (CSS) in patients with early‐stage breast carcinoma who underwent conservative surgery (CS) and received postoperative radiotherapy (RT).

Birth weight prediction by three-dimensional ultrasonography: fractional limb volume.

To introduce fractional limb volume as a new ultrasonographic parameter, validate reliability of fractional limb volume measurements, develop new birth weight prediction models, and examine their practical utility for estimating fetal weight during late pregnancy.

Prostate Volume Reduction With Androgen Deprivation Therapy Before Interstitial Brachytherapy

PURPOSE We assessed the degree of prostate downsizing using androgen deprivation, and determined its relation to clinical and pathological variables. MATERIALS AND METHODS From June 1994 to January 2000, 107 patients with prostate cancer received androgen deprivation before interstitial brachytherapy at our hospital. All charts were reviewed for clinical, pathological and treatment related variables. Prostate volume was measured using transrectal ultrasound. All variables were analyzed with regard to the degree of prostate downsizing. RESULTS Mean percent volume reduction of the prostate was 33% after a 3.7-month average duration of androgen deprivation. Larger prostate volume before androgen deprivation and longer deprivation duration statistically correlated with mean percent volume reduction. Simple linear and multiple regression analyses revealed that these 2 variables remained significant predictors of percent volume reduction. Subgroup analysis indicated that a significant difference was seen in patients who received androgen deprivation with luteinizing hormone releasing hormone agonists alone versus those who received treatment with total androgen blockade (luteinizing hormone releasing hormone agonists plus antiandrogens 30% versus 35%, p = 0.04), and when prostate volume before androgen deprivation was less than 50 cc versus larger volumes (30% versus 35%, p = 0.01). Of patients with an initial prostate volume of greater than 50 cc 82% achieved a volume of less than 50 cc after androgen deprivation therapy. CONCLUSIONS Androgen deprivation therapy before brachytherapy is a method of downsizing the prostate to overcome anatomical limitations, including larger gland volume and pubic arch interference.

Four-dimensional fetal echocardiography with spatiotemporal image correlation (STIC): A systematic study of standard cardiac views assessed by different observers

Objective. To test the agreement between observers and reproducibility of a technique to display standard cardiac views of the left and right ventricular outflow tracts from four-dimensional volume datasets acquired with Spatiotemporal Image Correlation (STIC). Methods. A technique was developed to obtain dynamic multiplanar images of the left ventricular outflow tract (LVOT) and right ventricular outflow tract (RVOT) from volume datasets acquired with STIC. Volume datasets were acquired from fetuses with normal cardiac anatomy. Twenty volume datasets of satisfactory quality were pre-selected by one investigator. The data was randomly assigned for a blinded review by two independent observers with previous experience in fetal echocardiography. Only one volume dataset was used for each fetus. After a training session, the observers obtained standardized cardiac views of the LVOT and RVOT, which were scored on a scale of 1 to 5, based on diagnostic value and image quality (1 = unacceptable, 2 = marginal, 3 = acceptable, 4 = good, and 5 = excellent). Median scores and interquartile range, as well as inter- and intraobserver agreement were calculated for each view. Results. The mean menstrual age at the time of volume acquisition was 25.5 ± 4.5 weeks. Median scores (interquartile range) for LVOT images, obtained by the first and second observers, were 3.5 (2.25–5.00) and 4 (3.00–5.00), respectively. The median scores (interquartile range) for RVOT images obtained by the first and second observers were 3 (3.00–5.00) and 3 (2.00–4.00), respectively. The interobserver intraclass correlation coefficient for the LVOT was 0.693 (95% CI 0.380–0.822), and 0.696 (95% CI 0.382–0.866) for the RVOT. For the intraobserver agreement analysis, observer 1 gave higher scores to the LVOT the second time the volumes were analyzed [LVOT: 3.50 (2.25–5.00) vs. 5.00 (4.00–5.00, p = 0.008)]. Conclusion. STIC can be reproducibly used to evaluate fetal cardiac outflow tracts by independent examiners. Slightly better image quality rating scores during the intraobserver variability trial suggests the presence of a learning curve for the manipulation and analysis of volume data obtained by STIC.

Nasal Bone Evaluation in Fetuses With Down Syndrome During the Second and Third Trimesters of Pregnancy

Objective. This study examined the use of three‐dimensional ultrasonography for evaluating the fetal nasal bone, as a sonographic marker of Down syndrome, during the second and early third trimesters of pregnancy. Methods. Forty fetuses, including 20 with trisomy 21, were scanned once by three‐dimensional ultrasonography. A midline sagittal view of the facial profile was used to analyze the volume data. Independent examiners reviewed blinded and randomly allocated volume data sets for the nasal bone. Interobserver reliability was evaluated for the sonographic presence or absence of the nasal bone. Logistic regression determined the contribution of this parameter to the presence of Down syndrome. Results. Both examiners showed substantial agreement in scoring whether the nasal bone was visualized by three‐dimensional ultrasonography (P < .001). They identified 40% to 45% of fetuses with abnormalities using the absence of the nasal bone as a sonographic marker. However, a substantial number of fetuses with abnormalities were also found to have a nasal bone present. The nasal bone was visualized in 80% to 90% of fetuses without abnormalities. Conclusions. Three‐dimensional ultrasonography can be used to evaluate the fetal nasal bone with substantial interobserver agreement during the second and early third trimesters of pregnancy. A nonvisualized nasal bone identified 40% to 45% of fetuses with Down syndrome in this study.

Second-Trimester Sonography and Trisomy 18

Objective. This report presents the findings seen on initial second‐trimester sonography in a large group of fetuses with trisomy 18. The object of this study was to describe the types and frequencies of abnormal sonographic findings seen and to further evaluate those cases in which no abnormal findings were noted. Methods. A retrospective chart review of the prenatal sonograms in cases of trisomy 18 was conducted. Results. Forty‐nine fetuses with trisomy 18 were examined by second‐trimester sonography. Multiple fetal anomalies were seen in most cases. The most frequent structural findings involved the brain (82%), heart (55%), and upper extremities (53%). Growth abnormalities occurred in 39% of these fetuses. Choroid plexus cysts were the most common individual findings. Larger cysts increased the likelihood of trisomy 18, although no fetuses with trisomy 18 had isolated choroid plexus cysts. Seven fetuses (14%) had no anomalies seen on their initial scans. In each of these scans, the fetal anatomy was incompletely visualized because of technical constraints. Six had subsequent scans approximately 2 weeks later, which showed abnormal sonographic findings. Conclusions. Most fetuses with trisomy 18 were identified by structural anomalies, typically seen in the brain, heart, and upper extremities. Larger choroid plexus cysts were associated with this aneuploidy. Technical factors, which limit fetal visualization, were noted in all cases in which no sonographic abnormalities were detected during the initial sonographic examinations. Detection of abnormal cases will rely on a completed evaluation of a routine fetal anatomic survey.

Second-Trimester Sonography and Trisomy 18 The Significance of Isolated Choroid Plexus Cysts After an Examination That Includes the Fetal Hands

Objective. To estimate the risk of trisomy 18 with the finding of isolated choroid plexus cysts after a standard sonographic examination that is extended to include the fetal hands. Methods. A retrospective chart review was performed on all fetuses with choroid plexus cysts on second‐trimester sonographic examinations. When choroid plexus cysts were identified, our standard protocol for fetal evaluation was expanded to include the hands. If no other findings were noted on completion of this examination, the choroid plexus cysts were classified as “isolated.” These results were correlated with the presence or absence of trisomy 18 to determine the impact of this approach for the detection of fetuses with this aneuploidy. Results. From March 1990 to the end of 2001, 49,435 fetuses that were subsequently delivered at our hospital were scanned between 16 and 25 menstrual weeks. At least 1 choroid plexus cyst was detected in 1209 fetuses (2.3%), of which 1060 were isolated. No fetuses with isolated choroid plexus cysts had trisomy 18. However, 3 fetuses with trisomy 18 had choroid plexus cysts and abnormal hands as their only abnormal findings. Conclusions. Fetuses with an apparently isolated finding of choroid plexus cysts can be further evaluated by extending the standard examination to include the hands. If no other findings are identified, the risk of trisomy 18 appears to be low.